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 .
1. The Amendment filed July 6, 2026 in response to the Office Action of February 6, 2026, is acknowledged and has been entered. Claims 1-3, 5-16, 20-22, and 24 are now pending. Claims 4, 17-19, 23, and 25 are canceled. Claims 1 and 5 are amended. Claims 1-3, 5-16, 20-22, and 24 are currently being examined as drawn to the elected species of:
A. gene signature consisting of the expression of six to 10 genes selected from: SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B; and
B. comparing gene signature expression to (1) an individual who is suffering from said hematology malignancy or of a population of such individuals.
The species C of CD123xCD3 antibodies including JNJ-63709178 are canceled upon cancellation of claim 17.
Maintained Rejection
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.
2. Claims 1-3, 5-16, 20-22, and 24 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature/ a natural phenomenon) without significantly more. The claim(s) recite(s) evaluating the expression of a gene expression signature consisting of six to ten genes selected from SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B in a cellular sample from a patient having a hematological malignancy prior to treatment with a CD123 x CD3 bispecific molecule, comparing the gene expression signature to the gene expression signature of an individual or population of individuals suffering from said hematologic malignancy, and identifying the patients as a suitable responder for treatment with the CD123 x CD3 bispecific molecule if the expression of said gene expression signature is found to be increased relative to said expression of said gene expression signature of the individual or population of individuals. Thus, the claims are directed to the judicial exception of gene expression correlated to response to treatment with a CD123 x CD3 bispecific molecule.
This judicial exception is not integrated into a practical application because the claims recite only the detection or observation of a naturally occurring phenomenon/law of nature, which is data gathering to observe the naturally occurring phenomenon/law of nature without applying the data to a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite general detection procedures to evaluate and observe naturally occurring gene expression levels. The steps of evaluating the expression of 6 to 10 genes selected from SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B in a patient having hematological cancer, as well as correlating to therapeutic responses, are considered known, routine steps and are typically taken by those in the field to perform testing of a sample and are not elements that are sufficient to amount to significantly more than the judicial exception (see MPEP 2106.05(d)). For example, McWeeney et al (Blood (2007) 110 (11) : 1007); Prince et al (Blood (2006) 108 (11) : 2715); Yan et al (Oncotarget, 2017, 8:1529-1540); and Boer et al (Haematologica, 2015, 100:e263) all teach and demonstrate utilizing commercially available Affymetrix U133 Plus 2.0 array to detect gene expression levels in hematologic cancer patients for comparison and correlation to therapeutic responses, wherein Affymetrix U133 Plus 2.0 array comprises detection of all of SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B genes, as well as ABCF1 (Affymetrix HG-U133 Plus 2.0 annotation files are located at https://www.thermofisher.com/order/catalog/product/900466). US Patent Application Publication 2021/0395374, Davidson et al; Rutella et al (Blood, November 2018, 132(Supplement 1):444); Uy et al (Blood, November 2018; 132(Supplement 1):764); Uy et al (Blood, November 2019; 134 (Supplement 1):733); and Vadakekolathu et al (Blood, November 2019, 134 (Supplement 1): 460) all demonstrate utilizing commercially available Nanostring PanCancer IO360™ array to detect gene expression levels in hematologic cancer patients for comparison and correlation to therapeutic responses to CD123xCD3 bispecific molecule treatment, wherein Nanostring PanCancer IO360™ array comprises detection of all of SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B, as well as ABCF1 (see attached list of genes detected by PanCancer IO360™ array from https://nanostring.com/resources/pancancer-human-io360-panel-gene-list/). Routine data gathering in order to observe a natural phenomenon/ natural principle does not add a meaningful limitation to the method as it would be routinely used by those of ordinary skill in the art in order to observe the natural phenomenon/ natural principle, and it fails to narrow the scope of the claims such that others are not foreclosed from using the law of nature/natural phenomenon. Methods of detecting natural phenomenon preempt all practical uses of it as others must use/detect the natural phenomenon to apply it to any other correlations, diagnosis, prognosis, therapeutic response, monitoring, etc.
Claims 7 and 8 recite the method further comprises administering a treatment dosage of said CD123 x CD3 bispecific molecule to said patient if the patient is determined to be a suitable responder to such treatment. Claims 7 and 8 do not recite a practical application of the judicial exception because the claims do not require definitively identifying the patient as a suitable responder to such treatment and administering said CD123 x CD3 bispecific molecule to said patient identified patient. The claims state that CD123 x CD3 bispecific molecule is only administered if the patient is determined to be a suitable responder to such treatment and no such determination was made in the claimed method. Therefore, the step of practically applying the judicial exception by administering said CD123 x CD3 bispecific molecule is not required for the claimed method.
To obviate the rejection, there must be at least one additional element or physical step that applies, relies on, or uses the natural principle so that the claim amounts to significantly more than the judicial exception itself. The claimed method currently fails to provide a practical application of the judicial exception and fails to add any elements that amount to significantly more than the judicial exception.
Examiner Suggestion: Amend claim 1 to recite:
“…
(b) detecting an increased expression of said gene expression signature from the patient relative to said expression of said gene expression signature of the individual or population of such individuals listed in (1)-(3);
(c) identifying the patient as a suitable responder for treatment with a CD123 x CD3 bispecific molecule; and
(d) administering said CD123 x CD3 bispecific molecule to the patient;
wherein said gene expression signature consists of the expression of from six to ten genes selected from: SERPINH1, NOTCH2, FCGR3 A/B, FRP1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B.”
Response to Arguments
3. Applicants argue the instant claims are patent eligible under 35 USC 101 at both 2A (prong 2) and 2B analysis steps.
Applicants argue that the claimed methods, as a whole, provide a practical application and thus are patent eligible under Step 2A, prong two. Applicants argue the claims integrate a judicial exception into a practical application. Applicants argue the specification discloses there is a need to treat hematological malignancy with CD123xCD3 bispecific antibodies, the specification discloses identifying patients that can potentially benefit from treatment with CD123xCD3 bispecific antibodies, and this is a practical application. The ability of the claimed method to identify patients as being amenable for the treatment of a hematologic malignancy using CD123 X CD3 bispecific binding molecules is also valuable as it allows a medical professional to only administer the immune modulating bispecific binding molecules to patients more likely to respond to treatment. Applicants argue that this is important as even highly targeted immune treatments may have some side effects. Applicants argue that a provider may make a greatly improved assessment of whether a probable treatment response is worth the risk of some side effects. Thus, an application of the claimed method addressed the unmet need for the treatment of hematologic malignancies, especially for refractory or relapsed hematologic malignancies, with the use of CD123 X CD3 bispecific binding molecules.
Applicants argue that the claimed methods are patent eligible according to step 2B analysis and amount to significantly more than the judicial exception. Applicants argue that the claimed method provides a way to determine if a patient is a suitable candidate for treatment with CD123 X CD3 bispecific binding molecules. Such CD123 X CD3 bispecific binding molecules represent a new line of therapy that has shown to be promising in the treatment of hematologic malignancies, such as AML, particularly AML that is refractive to other lines of treatment. See, e,g,, Specification as filed, [0060] to [0064]. Applicants argue that the claimed method meets an unmet need by identifying a subpopulation of patients that can be treated with this new line of therapy. The ability of the claimed method to identify patients as amenable for the treatment of a hematologic malignancy using CD123 x CD3 bispecific binding molecules is also valuable as it allows a medical professional to only administer the immune modulating bispecific binding molecules to patients more likely to respond to treatment. This is important as even highly targeted immune treatments may have some side effects. As such, a provider may make a greatly improved assessment of whether a probable treatment response is worth the risk of some side effects.
Regarding claims 7 and 8, Applicants argue that it is unclear how the Office is reading the claims to not require determination of a suitable responder to treatment with CD123 x CD3 bispecific molecule since both claims 7 and 8 depend from or refer to claim 1 and therefore incorporate all the features and limitations of claim 1. Claim 1 specifically recites that the method is for "determining whether a patient would be a suitable responder to the use of a CD123 X CD3 bispecific molecule to treat a hematologic malignancy" and part (b) of claim 1 specify how a patient is identified as a suitable responder, i.e., increased gene expression signature. Accordingly, the claims clearly indicate that the method of claim 1 is used to identify a suitable responder and can further comprise administering a treatment dosage of CD123 X CD3 bispecific molecule to said identified suitable responder. Additionally, as discussed above, claim 1 recited judicial exception into a practical application. Therefore, claims 7 and 8, which depend from or refer to claim 1, also recite judicial exception into a practical application. Applicants argue that the Office's interpretation of claims 7 and 8 is improper as the Office disregarded the dependency of the claims and did not consider the claim language of claim 1.
4. The arguments have been carefully considered but are not persuasive.
Claims are directed to a judicial exception (Step 2A prong one analysis):
The claimed method is drawn to a judicial exception (i.e., a law of nature/ a natural phenomenon) without significantly more, wherein the judicial exception is SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B gene expression correlated to response to treatment with a CD123 x CD3 bispecific molecule (see MPEP 2106.04 and in particular MPEP 2106.04(b)).
Claims do not integrate the judicial exception into a practical application (Step 2A prong 2 analysis):
Contrary to arguments, the claimed method does not integrate the judicial exception into a practical application (see MPEP 2106.04(d)). Examiner did not misread the claims. The claims are broader than Applicants are arguing. Claims 1, 7, and 8 recite a method comprising steps that are conditional, depending upon the results of evaluating the gene expression signature. The claims require evaluating expression of the gene signature consisting of six to ten genes selected from SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B in a cellular sample from a patient, however, identification of the patients as a suitable responder and administration of the CD123xCD3 bispecific antibody only occurs if the expression of the gene signature is found to be increased relative to the expression signature of the individual or population of such individuals listed in (1)-(3) occurs. There is no claimed requirement for the patients tested in step (a) of claim 1 to have the result of an increased gene expression signature relative to the expression signature of the individual or population of such individuals listed in (1)-(3), therefore the method is open to resulting in decreased, mixed, or increased gene expression signatures of the patients tested. The claimed method recites two possible outcomes resulting in two different methods:
Outcome (1): measuring SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B gene expression level signature and detecting levels that are NOT found to be increased relative to the expression signature of the individual or population of individuals listed in (1)-(3) of claim 1, no identification of suitable responder is made and no treatment is applied; and
Outcome (2): measuring SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B gene expression level signature and detecting levels that are increased relative to the expression signature of the individual o population of individuals listed in (1)-(3) of claim 1, identifying the patients as a suitable responder, and administering CD123xCD3 bispecific antibody.
In outcome (1), the judicial exception is not integrated into a practical application because the claims recite only the detection or observation of a naturally occurring phenomenon/law of nature, which is data gathering to observe the naturally occurring phenomenon/law of nature without applying the data to a practical application. In outcome (1), there is no treatment step, therefore there is no application of the judicial exception. The claims encompass a method that fails to practically apply the judicial exception.
Claims do not amount to significantly more than the judicial exception (Step 2B analysis):
Contrary to arguments, the claimed method does not amount to significantly more than the judicial exception (see MPEP 2106.05). In outcome (1) the claimed method recites a judicial exception (i.e., a law of nature/ a natural phenomenon) without significantly more (see MPEP 2106.05(d)). As stated in the rejection, the step of measuring the level of SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B gene expression commercially arrays are well known and routinely established to observe levels of SERPINH1, NOTCH2, FCGHR3 A/B, FPR1, FBP1, PDGFA, CRABP2, THBS1, ICOS, and CD8B gene expression in biological samples and do not amount to significantly more than the judicial exception. The claims do not recite any inventive concepts or improved methods for gene expression detection to amount to significantly more than the judicial exception. Applicants’ arguments are all directed at outcome (2) of the method that requires identifying a responder and administering CD123xCD3 antibody for treatment, however, the claims are not limited to this method and outcome.
Examiner provided a suggested amendment above (and previously of record) that limits the method to outcome (2) which practically applies the judicial exception and amounts to significantly more than the judicial exception.
5. All other objections and rejections recited in the Office Action mailed February 6, 2026 are hereby withdrawn in view of amendments. The rejection of claim 17 under 35 USC 112(a) written description is withdrawn in view of cancellation of claim 17.
6. Conclusion: No claim is allowed.
Conclusion
7. 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.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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