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 4/4/2023 are under consideration.
Election/Restrictions
Applicant’s election of Group II, claims 18-22, 24 and 26-28 in the reply filed on 10/30/2025 is acknowledged. 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)).
Applicant’s election of “measuring CD3 expression” in response to the election of species requirement in the reply filed on 10/30/2025 is acknowledged. 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Claims 1-4, 7 and 11-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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.
In the 10/30/2025 IDS, Non-Patent Literature Document Cite No 1 by Filipovic is lined through because it is a duplicate of a reference cited on a previous IDS.
Drawings
A petition for color drawings/figures was granted on 7/13/2023.
Specification
The disclosure is objected to because of the following informalities: in para. 52, the specification recites “TNFSF14” rather than “TNFRSF14” (emphasis added).
Appropriate correction is required.
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 28 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 claim 28, the claim states “or both” at the end of the claim. It is unclear which two elements are being required by the recitation of “both”.
Regarding claim 28, the claim recites “said PD-1/PD-L1 based immunotherapy”. The recitation lacks proper antecedent basis. Amending the claim to depend from claim 27 may aid in overcoming this rejection.
Claim Rejections - 35 USC § 103
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 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.
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) 18-22, 24 and 26-28 is/are rejected 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).
Claim 18 is drawn to a “method of determining suitability of a subject non-responsive to PD-1/PD-L1 based immunotherapy to be treated with an HVEM based immunotherapy”; however, the active method steps do not explicitly require determining any suitability. MPEP 2111.02 states:
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
Accordingly, the claim language of "determining suitability of a subject non-responsive to PD-1/PD-L1 based immunotherapy to be treated with an HVEM based immunotherapy" merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring: the active method steps of “receiving a sample”, “determining T cell levels in said sample” and “treating a suitable subject with an HVEM based immunotherapy”. Furthermore, claim 18 recites “thereby determining suitability of a subject non-responsive to PD- 1/PD-L1 based immunotherapy to be treated with an HVEM based immunotherapy”, which demonstrates that the above active method steps are sufficient to accomplish the goal set forth in the preamble, and no additional steps or elements are required.
Claim 18 recites “wherein T cell levels above a predetermined threshold indicates said subject is suitable to be treated by said HVEM based immunotherapy”. The clause sets forth a property of T cell levels, but does not require an active method step of “indicating” any suitability based on determined T cell levels.
Regarding claims 18, 24 and 26, Rosenblum teaches receiving a sample from a subject that is not responsive to anti-PD-1 monotherapy and determining the levels of tumor infiltrating T cells using CD3 expression (para. 78).
Rosenblum does not specifically teach treating a suitable subject with an HVEM based immunotherapy as set forth in claim 18.
However, Ren demonstrates that HVEM expression is negatively correlated with PDL1 expression (Fig. 2) and is also expressed in the context of melanoma (p. 116). Ren further teaches that not all patients respond to PD1/PD-L1 therapies (p. 115) as also observed by Rosenblum and targeting other immune checkpoints, including HVEM, may be beneficial (p. 119).
Lotze demonstrates the HVEM agonists targeting different regions and/or domains were known (para. 1002-1016). Lotze further teaches pairing PD-1/PD-L1 immunotherapy with TNFRSF agonists, such as HVEM agonists (para. 1194).
It would have been prima facie obvious to the ordinary artisan at the time of filing to have treated the patients of Rosenblum that are non-responders to anti-PD-1 monotherapy with a combination of HVEM agonists and PD-1/PD-L1 immunotherapy. One would have been motivated to do so because PD-L1 and HVEM expression are inversely correlated as demonstrated by Ren. Thus, it is likely that the patients of Rosenblum would respond to an HVEM agonists. By including PD-1/PD-L1 immunotherapy with the HVEM agonists, any PD-1/PD-L1 expression induced by immune activation would be counteracted.
Regarding claims 19, 20 and 21, Rosenblum teaches the “subjects” or patients suffer from a disease that is treatable with PD-1 based immunotherapy and HVEM based immunotherapy because the patients have the solid cancer melanoma (para. 79, 80).
Regarding claim 22, Rosenblum teaches the sample is a disease sample or biopsy of abnormal tissue/melanoma (para. 59, 78 and 79).
Regarding claims 27 and 28, it would have been prima facie obvious to have combined the HVEM agonist and PD-1/PD-L1 immunotherapy for the reasons detailed above.
Conclusion
No claims allowed.
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.
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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