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 .
Detailed Action
Summary
This is a Non-Final Office action based on the 17/766155 RCE filed 09/02/2026.
Claims 1, 5-6 & 8-24 have been elected and fully considered.
Claim 2-4, 7 are cancelled.
Claims 25-28 are withdrawn.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/02/2026 has been entered.
Claim Interpretation
With respect to Claim 1, the preamble states that “determining the ability of an individual to respond to a stimulus,” is done, but the claim body only claimed steps that are incubating and measuring. Therefore, from the actual claimed steps in the claim body, no judicial exception is claimed. The examiner does note that as broadly claimed, “determining…ability to response to a stimulus,” could in itself be determined to be an abstract idea. However, as the claim body steps again, which are the actual limiting part of the claim do not encompass a judicial exception, no 101 rejection is made. The examiner notes this though, so applicant is cognizant of the rejections that might be made, if the claim language changes.
Further, with respect to this, the examiner notes that though not claimed instantly, comparison steps can sometimes be considered to be abstract ideas, so if applicant adds this type of step to the claim to fix the 112 issues below then applicant should make sure the comparison is practically applied, and that the preamble and overall claim is adjusted to be a method for measuring or detecting and not “determining,’ as instantly claimed.
Claim Rejections - 35 USC § 112
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.
Claim 1 and 5-6 & 8-24 are 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.
With respect to Claim 1, the preamble is drawn towards “an invitro or ex vivo method for determining the ability of an individual to respond to a stimulus,” however there is no step of “determining an ability.” What applicant seems to mean is measuring or detecting response to a stimulus, and the claim has been interpreted as so. Further in Claim 1, it is unclear in the claim body how one measures “an ability to respond to stimulus,” as only one measurement step happens, and there is nothing claimed about what indicates, “an ability to respond,” or not.
The term “analogous” in claim 1 is a relative term which renders the claim indefinite. The term “analogous” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As different people reading the claim would take analogous to mean different things and therefore the term is unclear in the claim.
Claims 5-6 & 8-24 are rejected by virtue of their dependency on Claim 1.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 5-6 & 8-10, 12-14, 17-23 is/are rejected under 35 U.S.C. 103 as obvious by KUCHROO in US 20190255107 in view of ROGGE in US 20180267058.
With respect to Claim 1, KUCHROO teaches of a method of detecting dysfunctional immune cells and that the dysfunctional immune cells are detected by one or more markers including IFITM1(paragraph 0127), and differentially expressed TNFSF13B and CCR1 and TFGB1 and IFITM1 (Table 18, paragraph 0775). This reads on measuring/detecting 3 biomarkers, 1 from each of the lists contained in Claim 1. KUCHROO also teaches of incubation of a sample with a stimulus, wherein the stimulus can be anti-CD3 ( type of antibody analogous to a superantigen) (paragraph 0392, 0143) or enterotoxins including staphylococcal enterotoxin (paragraph 0190, 0478, 0480).
KUCHROO teaches of the sample is a whole blood sample (paragraph 0395). However, KUCHROO does not teach of incubating a whole blood sample before any other processing with a stimulus as instantly claimed.
ROGGE is used to remedy this. ROGGE teaches of methods of predicting and measuring immune responses when exposed to stimuli (abstract). ROGGE more specifically teaches of taking whole blood and putting it in a TruCulture tube in batches with a stimulus and then incubating (paragraph 0089). The stimulus can be an agent that stimulates the innate or adaptive immune response (paragraph 0009, 0013-0015, 0036-0042).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incubated a whole blood sample with a stimulus as is done in ROGGE in the method of KUCHROO due to the advantage the TruCulture assay used by MUHIE has shown as being a highly standardized ex vivo assay that preserves physiological cellular interactions in whole blood and allows for precise measurements of immune parameters, with and without stimulation (ROGGE, paragraph 0008).
With respect to Claim 5, KUCHROO teaches of a method of detecting dysfunctional immune cells and that the dysfunctional immune cells are detected by one or more markers including IFITM1(paragraph 0127), and differentially expressed TNFSF13B and CCR1 and TFGB1 and IFITM1 (Table 18). This reads on measuring/detecting 3 biomarkers, 1 from each of the lists contained in Claim 1.
With respect to Claim 6, KUCHROO teaches of the patient having had surgery (paragraph 0413, 0419, 0421).
With respect to Claim 8, KUCHROO also teaches of incubation of a sample with a stimulus, wherein the stimulus can be anti-CD3 (paragraph 0392), which is capable of binding with at least one type of antigen presenting cell and at least one type of adaptive immunity cell (T-cell or B cell).
With respect to Claim 9, KUCHROO teaches that the stimulus/modulating agent can be a superantigen which is staphylococcal enterotoxin B (paragraph 0190).
With respect to Claim 10, KUCHROO teaches that the stimulus/modulating agent can be a superantigen which is staphylococcal enterotoxin B (paragraph 0190).
With respect to Claim 12, KUCHROO also teaches of incubation of a sample with a stimulus, wherein the stimulus can be anti-CD3 (paragraph 0392, 0139). Anti-Cd3 is a molecule/stimulus that “allows,” direct activation of T lymphocytes through broadest reasonable interpretation as this doesn’t require any actual activation.
With respect to Claim 13, KUCHROO also teaches of incubation of a sample with a stimulus, wherein the stimulus can be anti-CD3 (paragraph 0392, 0139). Anti-Cd3 is a molecule/stimulus that is an antibody that can recognize and activate a receptor on the surface (CD3 receptor) of T lymphocytes, through broadest reasonable interpretation as this doesn’t require any actual activation.
With respect to Claim 14, KUCHROO also teaches of incubation of a sample with a stimulus, wherein the stimulus can be anti-CD3 (paragraph 0392, 0139).
With respect to Claim 17, KUCHROO also teaches of incubation of a sample with a stimulus, wherein the stimulus can be anti-CD3 (paragraph 0392). Any antibody can be considered- “for therapeutic purposes,” through broadest reasonable interpretation.
With respect to Claim 18, KUCHROO teaches of measuring expression of mRNA(0138).
With respect to Claim 19, KUCHROO teaches of measuring RNA expression using RT-PCR, hybridization and sequencing(paragraph 0222).
With respect to Claim 20, KUCHROO teaches of measuring RNA expression using RT-PCR, hybridization and sequencing(paragraph 0222).
With respect to Claim 21, KUCHROO teaches of measuring RNA expression using RT-PCR, hybridization and sequencing(paragraph 0222).
With respect to Claim 22, KUCHROO teaches of detecting and normalization with respect to housekeeping genes (paragraph 0770).
With respect to Claim 23, KUCHROO teaches of treating with a modulator or stimulus and of comparison with an untreated ( so unmodulated or unstimulated) control (paragraph 0481).
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as obvious over KUCHROO in US 20190255107 in view of ROGGE in US 20180267058in view of SCHETTINI in US 20150301058.
With respect to Claim 11, KUCHROO teaches that the stimulus/modulating agent can be a superantigen which is staphylococcal enterotoxin B (paragraph 0190), so reads on “analogous to a superantigen,” Staphylococcal Enterotoxin B (SEB) however is not a bispecific antibody.
ROGGE teaches of methods of predicting and measuring immune responses when exposed to stimuli (abstract). ROGGE more specifically teaches of taking whole blood and putting it in a TruCulture tube in batches with a stimulus and then incubating (paragraph 0089).
KUCHROO and ROGGE do not teach of using a bispecific antibody.
SCHETTINI is used to remedy this. SCHETTINI teaches of a method in which biomarkers are assessed for candidate treatments (abstract) and further teaches that one of the candidate treatments or stimulus can be bispecific antibodies (paragraph 0212, 0211).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use bispecific antibodies as is done in SCHETTINI in the method of KUCHROO and ROGGE due to the advantage these bispecific antibodies have for binding preferentially to two (bi) parts instead of one (SCHETTINI, paragraph 0212).
Claim(s) 15-16 is/are rejected under 35 U.S.C. 103 as obvious by KUCHROO in US 20190255107 in view of ROGGE in US 20180267058 in view of BORGLUM in US 20090297563.
With respect to Claim 15, KUCHROO and ROGGE teaches of the above but does not teach of using imidazoquinoline (paragraph 0392).
BORGLUM is used to remedy this and more specifically teach of using imidazoquinoline as an activator/stimulator of immune cells (paragraph 0035). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to stimulate with imidazoquinoline as is done in BORGLUM in the method of KUCHROO and ROGGE due to the advantage is has a being a potent activator/stimulator of immune cells (BORGLUM, paragraph 0035).
With respect to Claim 16, KUCHROO and ROGGE also teaches of the above but does not teach of using resiquimod (paragraph 0392). BORGLUM is used to remedy this and more specifically teach of using resquimod as an activator/stimulator of immune cells (paragraph 0035). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to stimulate with resquimod as is done in BORGLUM in the method of KUCHROO and ROGGE due to the advantage is has a being a potent activator/stimulator of immune cells (BORGLUM, paragraph 0035).
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as obvious over KUCHROO in US 20190255107 in view of ROGGE in US 20180267058 in view of RUSSWURM in US 20110098195.
With respect to Claim 24, KUCHROO and ROGGE teach of the above, but do not teach of comparison of ratios of expression.
RUSSWURM is used to remedy this and teaches that the expression data includes ratios of the expression values (paragraph 0382). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to calculate ratio of expression values as is done in RUSSWURM in the method of KUCHROO and ROGGE due to the advantage that this ratio value gives for indicating fold change and by what factor the transcript in one sample was expressed differently than in the other sample (RUSSWURM, paragraph 0382).
Response to Arguments
Applicant's arguments filed 09/02/2026 have been fully considered. They are persuasive in overcoming the prior grounds of rejection, however due to the instant amendments, a new grounds of rejection is shown above.
All claims remain rejected.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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