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 .
The amended claims filed 4/23/2026 are under consideration.
The amendments and arguments presented in the papers filed 4/23/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 1/28/2026 listed below have been reconsidered as indicated.
a) The objection of the specification is withdrawn in view of the Remarks (p. 6).
b) The rejection of claim 28 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendments.
c) The rejection of claim(s) 18-22, 24 and 26-28 under 35 U.S.C. 103 as being unpatentable over Rosenblum (US 2018/0055882 A1) in view of Ren (Lung Cancer. 2018. 125:115-120) and Lotze (WO 2018/129332 A1), are withdrawn in view of the amendments to the claims.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Election/Restrictions
Applicant elected Group II, claims 18-22, 24 and 26-28, in the reply filed on 10/30/2025. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election was treated as an election without traverse (MPEP § 818.01(a)).
Applicant elected “measuring CD3 expression” in response to the election of species requirement in the reply filed on 10/30/2025. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-4, 7 and 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/30/2025.
Priority
The present application is a continuation of PCT/IL/2021/051196 (filed 10/5/2021), which claims benefit to US provisional application 63/087,376 (filed 10/5/2020), and claims benefit to US provisional application 63/182,968 (filed 5/2/2021).
Priority to US provisional application 63/087,376 (filed 10/5/2020) is not recognized as it fails to disclose the method of claim 18.
The claims under consideration are given the earliest effective filing date of 5/2/2021, corresponding to US provisional application 63/182,968.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Drawings
A petition for color drawings/figures was granted on 7/13/2023.
Claim Objections
Claim 18 is objected to because of the following informalities: the preamble of the claim is not consistent with the active method steps of the claim. The active method steps involve treating a subject, while the preamble is focused on “determining the suitability of a subject”. Appropriate correction is required.
Claim 18 is objected to because of the following informalities: the claim recites a “thereby” clause stating “determining the suitability of a subject non-responsiveness to PD-1/PD-L1 based immunotherapy to be treated with an HVEM immunotherapy”. The claim is extraneous in view of newly added step (c). Appropriate correction is required.
Claim Interpretation
In claim 28, the claim is interpreted as follows:
wherein a)_said PD-1/PD-L1 based immunotherapy is PD-1 and/or PD-L1 blockade, b)_said HVEM based immunotherapy is HVEM blockade, or c) said PD-1/PD-L1 based immunotherapy is PD-1 and/or PD-L1 blockade and said HVEM based immunotherapy is HVEM blockade.
Claim Rejections - 35 USC § 112
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.
Claims 18-22, 26-27 and 31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The specification, while being enabling for:
A method of treating a subject who is non-responsive to PD-1/PD-L1-based immunotherapy with an HVEM-based immunotherapy, the method comprising:
receiving a tumor sample from said subject;
determining the levels of tumor infiltrating T cells in said tumor sample;
classifying the subject as suitable subject to be treated by said HVEM-based immunotherapy due to said determined levels of tumor infiltrating T cells being above a predetermined threshold; and
Treating said suitable subject with an HVEM-based immunotherapy,
does not reasonably provide enablement for the method of claim 18 in which any sample is used for determining the levels of any T cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The claims broadly encompass the use of any sample for determining the levels of any T cells. The instant specification only describes the analysis of tumor infilitrating T cells within tissue samples of tumors. See Examples 1 and 2.
The claims encompass the use of bodily fluids, blood, serum and/or plasma. Serum and plasma are prepared in a manner such that they are devoid of cells. Thus, using these samples would not provide information regarding T cells levels. While cell-free nucleic acids may provide information regarding T cell levels, there is no indication that the information is useful as it represents levels of T cells within the entire body. The T cell levels infilitrating tumors is the relevant information the instant specification bases a prediction on. There is no indication that the level of tumor infilitrating T cells is represented by nucleic acids found within tumors.
Regarding samples like other bodily fluids such as urine or saliva or other tissues samples obtained via biopsy, such as healthy tissues or necrotic tissue, there is no indication that T cell levels in these non-tumor tissue have any relevancy. Based on the data provided, it is the T cell levels within the tumor itself that are relevant as they are the cells that will respond and attack tumor cells.
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 31 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.
Regarding new claim 31, the claim recites “before said determining, comparing said subject's determined T cell levels to said predetermined threshold level of T cells”. The only “determining” is done in regards to “T cell levels in said sample”. The recitation lacks proper antecedent basis as the “comparing” requires the “subject’s determined T cell levels” but the “comparing” is explicitly performed before that information is determined. Amending the claim to recite “after said determining” may overcome this issue.
Allowable Subject Matter
The following claim would be allowable:
A method of treating a subject who is non-responsive to PD-1/PD-L1-based immunotherapy with an HVEM-based immunotherapy, the method comprising:
receiving a tumor sample from said subject;
determining the levels of tumor infiltrating T cells in said tumor sample;
classifying the subject as a suitable subject to be treated by said HVEM-based immunotherapy based said determined levels of tumor infiltrating T cells being above a predetermined threshold; and
treating said suitable subject with an HVEM-based immunotherapy.
If the claims are amended to adopt the above claim language, it is suggested that the dependent claims be amended for any antecedent basis issues.
Conclusion
No claims 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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