DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/25/2025 has been entered.
Claims 1-88 have been cancelled. Claims 89-93 are new.
Claims 89-93 are pending and under examination.
2. All rejections pertaining to claims 77 and 86-88 are moot because the claims were cancelled with the reply filed on 8/25/2025.
New grounds of rejection are set forth below.
Claim Objections
3. Claim 90 is objected to because of the recitation “a normal range” in the last line. Correction to “the normal range” is required.
4. Claim 93 is objected to for being dependent upon itself. Appropriate correction is required.
5. Claim 93 is objected to for the recitation “a basal level”. Correction to “the basal level” is required.
New Rejections
Claim Rejections - 35 USC § 112, first paragraph – new matter
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
7. Claims 89-93 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. 37 CFR 1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application".
Specifically, the recitation in the new claims 89-93 of an “in vitro method for detecting a pathological condition characterized by abnormal T cell proliferation” by analyzing the activation and/or inhibition of GSK-3β, p38, Erk, PI-3K, and PKC in the abnormal T cell is considered new matter.
Even not specifically recited, the claimed diagnosis by measuring activation or inhibition of GSK-3β, p38, Erk, PI-3K, and PKC in T-cells necessarily entails isolating the T-cells from a sample obtained from a patient in need of diagnosis. This is not supported by the specification and original claims. The specification and the original claims only contemplate practicing the diagnosis method with biological samples isolated from a patient, where the biological sample is a tissue or a biological fluid sample; the activation and expression levels are determined in the tissue or biological fluid sample, not in T-cells isolated from the sample (assessing inactivation is only supported for GSK-3β). See the specification (p. 2, second to last paragraph; p. 5, fourth paragraph; p. 7, first paragraph; paragraph bridging p. 10 and 11; p. 11-12; p. 14; p. 16-17); see the original claims. Nowhere does the specification contemplate using T-cells isolated from a patient’s sample for diagnosis.
Although the applicant points to Example 4 (results shown in Fig. 8) for support. However, a diagnosis method entails using cells isolated from a patient, without further manipulating them with inhibitors or activators in vitro. Example 4 is drawn to experiments aimed at better understanding the role played by Gsk3β in T-cell proliferation. The experiments are performed with T-cells (not from a patient in need of diagnosis), which are manipulated in vitro with inhibitors of p38, Erk, and PI-3K together with a PKC inhibitor or activator. The conclusion drawn from this experiment is that phosphorylated GSK-3β sites could be used to monitor the activation state of GSK-3β for diagnostic purposes. Clearly, Example 4 does not provide support for diagnosis via determining inhibition of p38, Erk, PI-3k together with PKC inactivation/activation, The remaining of the specification does not provide support for the embodiment under rejection.
Furthermore, claim 90 recite that Gsk3β inactivation is characterized by increased pGsk3β levels if the total Gsk3β is within the normal range. There is nothing in the specification supporting this recitation.
MPEP 2163.06 notes "If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981)." MPEP 2163.02 teaches that "Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes "When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not "new matter" is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure".
Claim Rejections - 35 USC § 112, first paragraph – enablement
8. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
9. Claims 89-93 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for detecting abnormal T-cell proliferation by determining the activation or inhibition of Gsk3β, does not reasonably provide enablement for detecting abnormal T-cell proliferation by detecting: (i) p38, Erk, and PI-3k inhibition and unaffected PKC; (ii) p38, Erk, and PI-3k inhibition and activated PKC; and (iii) p38, Erk, PI-3k and PKC inhibition. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make or use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC § 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988).
Wands states on page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skills of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The specification teaches by exemplification in vitro manipulating T-cells (not from a patient in need of diagnosis) by treating them with inhibitors of p38, Erk, and PI-3K together with/without a PKC inhibitor or activator. The goal of the experiment is to determine the effect of PKC on GSK-3β and T-cell proliferation. The data show that (i) inhibiting p38, Erk, and PI-3k while leaving PKC unaffected results in reduced T-cell proliferation; (ii) inhibiting p38, Erk, and PI-3k while activated PKC does not significantly change T-cell proliferation; and (iii) inhibiting all of p38, Erk, PI-3k and PKC results in reduced T-cell proliferation. The conclusion drawn from this experiment is that phosphorylated GSK-3β sites could be used to monitor the GSK-3β activation state for diagnostic purposes.
The claimed diagnosis method necessarily requires using T-cells isolated from a patient and determining naturally occurring changes in these cells, i.e., without further in vitro manipulation via treatment with inhibitors of p38, Erk, and PI-3k together with PKC inhibitors/activators. There is nothing in the specification or the art indicating that the claimed changes in p38, Erk, PI-3k and PKC (observed by manipulating T-cells in vitro with inhibitors/activators) would naturally occur in patients’ unmanipulated T-cells. Just because T-cells are treated in vitro with inhibitors/activators does not mean that all the ensuing changes are replicated in the T-cells isolated from any patient affected by any pathological condition associated with abnormal T-cell proliferation. The art provides evidence to the contrary. For example, Yiasere et al. (J. Virol., 2003, 77: 10900-10909) teach that T-cells in HIV patients are characterized by reduced proliferation (see Abstract). Furler et al. (Immunol. Res., 2010, 48: 99-109) teach that p38 and Erk are activated in the T-cells from HIV patients (see Abstract; p. 101-102).
Based on the teachings in the art and lack of guidance in the specification, one of skill in the art would not conclude and would require undue experimentation to determine whether inhibition of p38, Erk, and PI-3k with or without PKC inhibition/activation occurs in patient’s T-cells and whether it can be used to detect a pathological condition characterized by abnormal T-cell proliferation as claimed.
Claim Rejections - 35 USC § 112, 2nd paragraph
10. 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.
11. Claim 93 is 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 93 recites the limitation "said activation and/or inactivation" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
12. 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
13. Claims 89-93 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Tang et al. (Cell Cycle 2009, 8: 2789-2793), in view of Cahn et al. (Transplantation, 1995, 60: 939-042; Abstract).
Although independent claim 89 recites determining the activation and/or inactivation of GSK-3β, p38, Erk, PI-3K, and PKC, the following wherein clauses do not require determining the activity of all GSK-3β, p38, Erk, PI-3K, and PKC; the wherein clauses are distinct embodiments not capable of being used together in the claimed detection method. The rejection addresses the first wherein clause which only requires determining GSK-3β inactivation.
Tang et al. teach that systemic lupus erythematosus (SLE) is characterized by the activation and proliferation of T-cells. Tang et al. teach isolating T-cells from patients with systemic lupus erythematosus and assessing them for the Akt phosphorylation level (Akt473) and Gsk3β; assessing takes place via Western blotting with antibodies against the phosphorylated and unphosphorylated Akt and Gsk3β; the level of Gsk3β phosphorylated at Ser9 (i.e., inactivated) is increased compared to the control, while the total Gsk3β level is not changed compared to the control (claims 89-91 and 93) (see Abstract; p. 2789, paragraph bridging columns 1 and 2; p. 2790, column 1; p. 2790, Fig. 2; paragraph bridging p. 2791 and 2792).
Although Tang et al. do not teach diagnosing, one of skill in the art would have reasonably concluded that determining Gsk3β inactivation in T-cells could be used for diagnosis. One of skill in the art would have found obvious to isolate T-cells from subjects suspected of being affected by SLE and further determine their inactivated Gsk3β level and increase in proliferative capacity, with the reasonable expectation that doing so would determine whether the subjects have SLE. By using T-cells isolated from different subjects, one of skill in the art would have reasonably expected to identify different increase proliferative rates, depending on the severity of the disease. With respect to the proliferative level being increased by at least 20% (claim 89), as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
With respect to claim 89, one of skill in the art would have found obvious to assess Gsk3β inactivation in the T-cells at different time points to assess disease progression or therapeutic effect in case therapy is given to the subjects, as doing so was routine in the prior art (see Cahn et al., Abstract).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
14. The arguments do not pertain to the new rejections.
15. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633