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
Applicant’s election without traverse of Group I, now claims 1-8 and 87-89 in the reply filed on 1/21/2026 is acknowledged.
Claims 49, 50, 53, 57-59, 78, 80 and 83 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/21/2026.
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 1-8 and 87-89 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a method with an abstract idea without significantly more. The claim(s) recite(s) “comparing the test biomarker profile to a reference biomarker profile comprising the level(s) of the same at least one biomarker; identifying the subject as having or predicting that the subject will have a toxic response and/or dysfunctional response non-response to an immunomodulatory treatment when the test biomarker profile comprises increased levels of the at least one biomarker as compared to the reference biomarker profile”.
This judicial exception is not integrated into a practical application because the additional steps, such as measuring a level of at least one biomarker, selecting a therapeutic agent to administer to the subject and administering to the subject a therapeutically effective amount of the therapeutic agent are being viewed as mere data gathering steps.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps of measuring and administering are common in the art (as noted in the rejections below).
Furthermore, it is noted that data gathering to be used in the abstract idea is insignificant extrasolution activity, and not a particular practical application. See MPEP 2106.05(g).
The examiner notes that office policy (per the July 2015 Interim Eligibility
Guidance with regards to USC 101 rejections) states that abstracts ideas may be ideas themselves and that one specific example of an abstract idea is the idea of comparing new and stored information (such comparing the measured levels at least one biomarker, like IL-18, IL-18BP, CD161+, etc) and using rules to identify whether or not the level of the at least biomarkers indicative of a patient/subject having a toxic and/or dysfunctional response to an immunomodulatory treatment.
In addition, the examiner notes that following the procedure outlined in Mayo
Collab. Svcs. v. Prometheus Labs (SCOTUS) 101 USPQ2d 1961, 132 S. Ct. 1289 (2012) that claim 1 (and therefore its dependent claims as well) would be ineligible since in step 1 it is noted that the claims are directed towards one of the statutory categories (i.e. “method of selecting a therapeutic agent to administer to a subject”) (as claimed in claim 1), while in step 2a it is noted that the claim is directed to a judicial exception (an abstract idea, as described above as the comparing and identifying steps) and in step 2b it is noted that the claims do not recite additional elements that amount to significantly more than the judicial exception since the additional administering and measuring steps are simply mere data gathering steps.
Therefore claims 1-8 and 87-89 are ineligible.
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.
Claim(s) 1-3, 5, 6 and 87 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al US 2019/0277858), as cited on the IDS.
Regarding Claims 1 and 6, Li et al teaches a method of selecting a therapeutic agent to administer to a subject, comprising obtaining a biological sample derived from a subject (see abstract and [0006]);
measuring a level of at least one biomarker selected from the group consisting of interleukin (IL)-18; IL-18 binding protein (IL-18BP), interferon gamma (IFNy), and CD161+ cells to generate a test biomarker profile (specifically interferon gamma or IL-18) (see [0080], [0133] and [0201]) ;
comparing the test biomarker profile to a reference biomarker profile comprising the level(s) of the same at least one biomarker (see [0006], [0112], [0124], [0131] and [0143]);
identifying the subject as having or predicting that the subject will have a toxic response and/or dysfunctional response non-response to an immunomodulatory treatment when the test biomarker profile comprises increased levels of the at least one biomarker as compared to the reference biomarker profile (see [0131], [0143] and [0242]);
selecting a therapeutic agent to administer to the subject, wherein the therapeutic agent comprises an anti-CD161 antibody, an anti-IL-18 antibody, an anti-IFNy antibody, an IL-18BP, or a combination thereof; and administering, to the subiect, a therapeutically effective amount of the therapeutic agent (such as CAR-T cell immunotherapy)(see [0111], [0115], [0124] and [0464]-[0465]).
Regarding Claim 2, Li et al teaches that the reference biomarker profile is from a subject or a population of subjects having a functional response (i.e. normal) to the immunomodulatory treatment with limited or no neurotoxicity (NTX) (see [0143], which discloses "In some cases, such reference value can be or is predetermined or known prior to performing the method, such as from a plurality of subjects previously treated with a cell therapy and assessed for the correlation of the parameter of the biomarker or, individually, each of the biomarkers in a panel to the presence of a toxic outcome (e.g. the presence of neurotoxicity, such as severe neurotoxicity and/or CRS, such as severe CRS)"; and [0146] , which recites that "the reference level is an average level of a group of subjects receiving the same treatment, e.g., for the same indication, and/or such subjects that do not develop the toxicity outcome, such as do not develop grade 3 or higher neurotoxicity").
Regarding Claim 3, Li et al teaches that the biological sample comprises a blood sample and/or a cell or tissue sample (see [0077] and [0165]).
Regarding Claim 5, Li et al teaches that the biological sample is obtained 1-30 days after the immunomodulatory treatment has initiated (see [0012]-[0013]), and wherein the at least one biomarker is selected from the group consisting of IL-18, IL-18BP, and IFNy (specifically interferon gamma or IL-18) (see [0080], [0133] and [0201]).
Regarding Claim 87, Li et al teaches the method of claim 11, wherein the level of the at least one biomarker of (A) is increased 1.1-fold to 10- fold as compared to the level of the same at least one biomarker of the reference biomarker profile (see [0008], which recites "In some cases, the relative value is a percentage or fold increase or percentage or fold decrease, compared to the reference value"; and [0229], which recites "outcomes associated with CRS include one or more of elevation of cytokines, such as a max fold change, e.g., of at least at or about 75, compared to pre-treatment levels of at least two cytokines").
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al as applied to claim 1 above, and further in view of Pfifer et al (US PGPub 2016/0215048).
Regarding Claim 4, Li et al teaches that the biological sample is obtained before the immunomodulatory treatment (see [0006] and [0125]), and that the at least one biomarker may be interferon gamma or IL-18) (see [0080], [0133] and [0201]).
However, Li et al does not explicitly disclose that the biomarker is selected from IL-18BP and/or CD161+ cells.
However, in the analogous art of means and methods for treating Interleukin 18 (IL-18)-associated diseases, Pfeifer et al teaches that the quantification of IL-18 levels in body fluids is usually performed by using ELISA assays, which comprise antibodies that are unspecific for the detection of free IL-18. The result achieved by ELISA assays is limited by the specificity of the used primary antibody, which binds the target antigen. Up to date it is merely possible to detect total IL-18 levels by using the commercially available antibodies, but no antibodies to free IL-18 are known so far. The detection of total IL-18 is inadequate for the assessment of free IL-18 levels, since IL-18 bound in a complex, e.g. bound to its natural antagonist IL-18 binding protein (IL-18BP) has a reduced affinity to IL-18 receptor. Further, it is known, that increased IL-18 levels often are associated with elevated IL-18BP levels (see [0003]). Furthermore, Pfeifer et al teaches that the IL-18BPspecific antibodies according to the present invention are able to reduce and/or abrogate the binding of free IL-18 to its receptor and to provide therapeutic benefits to patient suffering from an IL-18 associated disease or disorder (see [0008]). It would have been obvious to one of ordinary skill in the art to utilize IL-18BP specific antibodies for the benefit of enabling the patient/subject to reduce and/or abrogate the binding of free IL-18 to its receptor and to provide therapeutic benefits to patient suffering from an IL-18 associated disease or disorder.
Claims 4 and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al as applied to claim 1 above, and further in view of Salvetti et al (WO 2008065694).
Regarding Claim 4, Li et al teaches that the biological sample is obtained before the immunomodulatory treatment (see [0006] and [0125]), and that the at least one biomarker may be interferon gamma or IL-18) (see [0080], [0133] and [0201]).
However, Li et al does not explicitly disclose that the biomarker is selected from IL-18BP and/or CD161+ cells.
However, in the analogous art of biomarkers useful as diagnostic and therapeutic targets in demyelinating pathologies, in particular in multiple sclerosis, Salvetti et al teaches the use of CD161+ as the biomarker, wherein the CD 8+ T lymphocytes of patients affected by MS have a significant increase in the expression of CD 161 protein on the cellular membrane, with respect both to the healthy subjects and to the patients with RA (see page 9, lines 4-24). It would have been obvious to one of ordinary skill in the art to utilize CD161+ as the biomarker for the benefit of enabling effective diagnosis of MS.
Claim 89 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al as applied to claim 1 above, and further in view of Turtle et al (US PGPub 2011/0059012), cited on the IDS.
Regarding Claim 88, Li et al does not teach that the at least one biomarker comprises CD161+ cells, the method further comprising determining that the level of the CD161+ cells of the test biomarker profile is 10% to 30% of total live cells in the sample.
However, in the analogous art of identification and isolation of viable putative long-lived antigen-specific memory CD8.sup.+ T cell subsets (CMhi and EMhi) with high surface expression of CD161 and/or IL-18R.alpha, Turtle et al teaches the use of CD161+ as the biomarker and that high CD161 and/or IL-18R.alpha. expression may be used to identify human Rh123 effluxing long-lived memory cells in the CM and/or EM CD8.sup.+ T cell compartments. These populations may be useful as a source of T cells for adoptive immunotherapy, gene delivery or as targets for ablation in autoimmune or other immunopathologic conditions (see [0051]). In addition, Riddle et al teaches that the cells with CD161+ are considered enriched and the enriched cells constitute at least 1, 5, 10, 20, or 30 percent of the total cells in the preparation (see [0099]). It would have been obvious to one of ordinary skill in the art to utilize enriched cells having CD161+ (of 10-30%) as the biomarker for the benefit of effectively identifying human Rh123 effluxing long-lived memory cells in the CM and/or EM CD8.sup.+ T cell compartments. Furthermore, these populations may be useful as a source of T cells for adoptive immunotherapy, gene delivery or as targets for ablation in autoimmune or other immunopathologic conditions (see [0051] of Riddle et al).
Allowable Subject Matter
Claims 7-8 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims, assuming the 35 USC 101 rejections were overcome.
Regarding Claim 7, the prior art neither teaches nor fairly suggests removing CD161+ cells from an apheresis product obtained from the subject prior to the immunomodulatory treatment to produce an apheresis product reduced in CD161+ cells.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Albertson et al (US PGPub 2022/0088070) discloses adoptive cell therapy involving the administration of doses of cells for treating subjects with disease and conditions such as certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) (see abstract). In addition, Albertson et al teaches that the cytokines (i.e. biomarkers) measured include interferon gamma (IFNγ), GM-CSF, IL-6, IL-10, Flt-3L, fracktalkine, and IL-5, and/or tumor necrosis factor alpha (TNFα))(see [0377]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER WECKER whose telephone number is (571)270-1109. The examiner can normally be reached 9:30AM - 6 PM EST M-F.
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/JENNIFER WECKER/ Primary Examiner, Art Unit 1797