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 .
Response to Amendment
Claims 1-4 have been amended as requested in the amendment filed on 20 November 2025. Following the amendment, claims 1-17 are pending in the instant application. Applicant has elected the combination of Serine and Citrulline as the “at least one blood metabolite” for initial prosecution.
Claims 5-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 1-4 are under examination in the instant office action.
Claim Rejections - 35 USC § 112 (Maintained; New, Necessitated by Amendment)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4 stand as rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is still indefinite wherein it recites “using” either a concentration value or a value of a formula. In Remarks filed 20 November 2025, Applicant argues the amendment obviates the rejection by now reciting an active step of treating (“treating with the immune checkpoint inhibitor the subject identified as having a low risk of an adverse effect to the immune checkpoint inhibitor based on the evaluation”). This is not persuasive to overcome the rejection because the claim still fails to state what processes are encompassed by “using” the concentration value of at least one metabolite, or a value of a formula calculated “using” the concentration value, and how this leads to identifying a subject as having low risk of adverse effects. A person having ordinary skill in the art would not know when a concentration value indicates risk , or when a method comprising evaluating amino acid concentration values directly infringes the claimed method.
Claim 1 is further indefinite wherein it recites, “an explanatory variable to be substituted with the concentration value”. On page 7 of Remarks, Applicant asserts, “the term ‘explanatory variable’ is well-known to those of ordinary skill in the art – used to explain, predict or influence changes in another variable, known as the response variable.” This is not persuasive because the claim does not make clear how the formula including the explanatory variable substituted for the concentration are used to indicate risk of adverse effect. It is unclear what active steps are encompassed by the term “using”. A skilled artisan would not know what uses of the concentration value provide for identification of the subject as having low risk, nor what process would infringe upon this method. The rejection is maintained.
As currently amended, Claim 1 recites the term “low risk” that is a relative term which renders the claim indefinite. The term “low” is not defined by the claim itself, nor does the specification provide a standard for ascertaining the requisite degree (i.e. low v. intermediate v. high). The specification discusses comparing the concentration values (which may be the ratio or difference) to preset thresholds, however, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975) and MPEP 2173.05(q). Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
These rejections affect the scope of all depending claims, and therefore claims 2-4 are included in the rejection.
As currently amended, Claim 3 is indefinite wherein it recites blood is taken before treatment with an immune checkpoint inhibitor (ICI) is started, and the evaluating further comprises evaluating a risk of developing an adverse effect with the treatment. It is entirely unclear what processes are involved in the process of evaluating risk, or how a concentration value of at least one metabolite indicates risk of developing an adverse effect to ICI treatment. A person having ordinary skill in the art would not be reasonably apprised as to the metes and bounds of the method, nor when it is directly infringed.
Claim Rejections - 35 USC § 101 (Maintained)
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.
The rejection of Claims 1-4 under 35 U.S.C. 101 is maintained because the claimed invention is directed to a judicial exception without significantly more, for reasons of record in the prior Office action.
On page 8 of Remarks (Id), Applicant asserts the revised claim set obviates this rejection.
This is not persuasive to overcome the rejection of record. First, the newly added limitations of claims 2 and 3 recite, “evaluating further comprises evaluating”. The “evaluating” of these claims is a Mental Process as defined as – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III), and this is one of the enumerated groupings of abstract idea exceptions to patent-eligible subject matter. There are no added steps/elements in these claims that integrate this judicial exception into a practical application thereof.
The independent claim, Claim 1, has been amended to recite the additional step of “treating with the immune checkpoint inhibitor the subject identified as having a low risk of an adverse effect to the immune checkpoint inhibitor based on the evaluation”. One way to demonstrate integration into a practical application is when the additional elements apply or use the recited judicial exception to effect a particular treatment for a disease or medical condition. This new limitation, however, is not directed to a particular treatment in accordance with MPEP 2106.04(d)(2). The guidance states “that in order to qualify as a ‘treatment’ or ‘prophylaxis’ limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition” (emphasis added). First, the method of the instant claim does not treat or effect treatment of any specific disease. Second, the added “treating” limitation is a contingent limitation. The method of the invention requires a concentration value of at least one of the listed blood metabolites is used to identify a subject as having a low risk of an adverse effect to the immune checkpoint inhibitor, and if low risk is identified, then the subject is treated with the immune checkpoint inhibitor. The method of the invention does not affirmatively recite an action that effects a particular treatment; rather it conditionally recites continuing treatment. This limitation does not integrate the judicial exceptions (Abstract Ideas of “evaluating” and “using a concentration value”, or “using a value of a formula calculated using the concentration value”) into a practical application. (STEP 2A, Prong Two: NO)
In the previous action the Examiner provided evidence that the steps/elements recited in addition to the judicial exceptions were well-understood, routine, and conventional activities in the art before the effective filing date of the application. The newly added step of treating with the immune checkpoint inhibitor, was also routine within the art before filing. The following prior art teaches, “Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials” (Abstract; Darvin et al., Experimental & Molecular Medicine (2018) 50:165). Therefore, the steps/elements recited in addition to the judicial exception(s), alone or in combination, do not make an inventive contribution over the methods that were known in the art prior to filing. (STEP 2B: NO).
For all of these reasons, Claims 1-4 are directed to the judicial exception without significantly more and stand as rejected under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102 (Maintained)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-4 stand as rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bi et al., 2017 as evidenced by Shimbo et al, 2009, for reasons of record in the prior Office action.
On page 8 of Remarks (Id), Applicant argues Bi does not teach or suggest the new limitation of “treating with the immune checkpoint inhibitor the subject identified as having a low risk of an adverse effect to the immune checkpoint inhibitor base on the evaluation.”
This is not persuasive to overcome the rejection of record. As stated above, the newly added limitation of treating with an immune checkpoint inhibitor is contingent upon the subject being identified as having a low risk of an adverse effect. Absent that identification, there is no treating step. Further, the claims explicitly read upon evaluating the blood sample before the treatment, therefore it reads upon evaluating a concentration value of a claimed metabolite in any individual.
The Examiner maintains the position that the Bi et al. prior art discloses methods comprising determining the concentration value of plasma-free amino acids (PFAA). Bi et al. use AminoIndex Cancer Screening (AICS) technology to evaluate levels of amino acids in blood samples. In order to build AICS, 19 amino acids including threonine (Thr), asparagine (Asn), Ser, Gln, Pro, Gly, Ala, citrulline (Cit), Val, Met, Ile, Leu, Tyr, Phe, His, tryptophan (Trp), ornithine (Orn), Lys and Arg, were measured and statistically analyzed (pg. 2, paragraph, third paragraph). Table 1 of the Bi et al. reference discloses multiple studies in which PFAA concentration values were determined and alterations in the instantly-elected biomarkers Serine and Citrulline.
The Shimbo et al. reference is relied upon solely as evidence that the studies disclosed in Bi et al. utilize an “Agilent 1100 series liquid chromatography system (pg. 1485, section on HPLC/ESI-MS/MS analysis) and the AppliedBio-systems-MDS Sciex Analyst 1.4 software was used (pg. 1486, first paragraph). This teaches a control unit of an information processing apparatus, as required by instant Claim 4.
Therefore, the invention fails to distinguish over methods disclosed in the prior art, and Claims 1-4 are rejected.
Conclusion
No claim is allowed.
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.
Conclusion
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/STACEY N MACFARLANE/ Examiner, Art Unit 1675