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 .
1. Formal Matters
A. Applicant’s election without traverse of Group I in the reply filed on 5/27/26 is acknowledged. Therefore, this restriction is deemed proper and is made FINAL. No species election pertains to these claims.
B. Claims 1-87 are pending. Claims 6, 8, 9 and 15-87 are withdrawn as being drawn to non-elected inventions. Claims 1-5, 7 and 10-14 are the subject of this Office Action.
2. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors, embedded hyperlinks, or improperly referenced trademarks. Applicants’ cooperation is requested in correcting any errors of which Applicants may become aware.
3. 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.
A. Claims 1-5, 7, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Phosphogam (WO 2020/065584) in view of Burjanadze et al. Both references are cited on the IDS filed 1/16/24.
The claims are essentially drawn to a method of selecting a donor for gd T cell-based therapy based on the expansion capacity of cells from a subject.
Regarding claims 1,7 and 10, Phosphogam teaches a method of selecting a donor for gd T cell-based immunotherapy by assessing the anti-tumor activity of a population of gd T cells from a subject and selecting a donor based on this activity (page 13, line 23 to page 14, line 2). They teach that “some donors may be more effective against certain classes of cancers or even against a specific type of cancer” (page 12, lines 26-31). This activity can be viewed as assessing the immune phenotypes of the T cells. Phosphogam does not teach expansion.
However, Burjanadze does teach the evaluation of the expansion capacity and cell cytotoxicity of circulating gd T cells from MM patients and that culturing PBMN cells with Phosphostim and IL-2 triggered a 100-fold expansion of gd T cells in 78% of newly diagnosed patients (Abstract). These expanded T cells had a high ability to kill cancer cells, but not normal cells. Burjanadze does not teach a method of selecting a donor for gd T cell-based immunotherapy.
Therefore, it would have been obvious at the time of the invention to have used the method of Phosphogam, which focuses on selecting a donor gd T cell population for immunotherapy in a subject/patient based on anti-tumor activity, along with the method of Burjanadze, which teaches expansion of gd T cells. Given that the aim of both references is to treat cancer is a patient by using gd T cells identified as therapeutically useful, it would have been obvious to have identified this population of gd T cells from a donor and then expand them to exploit their numbers and ability to treat a given cancer.
Regarding claims 2 and 3, Burjanadze teaches (page 207, left column, first full paragraph) -
The aim of this study was to compare the ability of Phosphostim and Zoledronate to expand gd T cells fromnormal donors or patients with MM and to evaluate their vitro anti-MMC cytotoxicity of Phosphostim-expanded gd T cells from patients with MM.
Regarding claims 4 and 5, Burjanadze does not specifically teach an “index score”; however, the reference does teach calculations were used to measure “successful amplification” and that “a strong correlation of amplification rates with Phosphostim and zoledronate was found” (page 209 under “Expansion of gd T Cells with Phosphostim”). Given this, it would have been obvious at the time of the instant invention to have performed such calculation in order to optimize a donon/subject protocol for the highest probability of success/treatment. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
Regarding claim 11, if not a product of the procedure, it would have at least been obvious to have chosen a cell line with both central and effector T cells in order to provide maximum overall protection (e.g, blood, peripheral tissues, lymph nodes of the patient).
B. Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Phosphogam in view of Burjanadze et al., further in view of (1) Buchbinder and Desai, (2) Li et al., (3) Ribas and Grasso, (4) Trapani et al. and (5) Jeannin et al.
The teachings of Phosphogam and Burjanadze are seen in paragraph A of this section. Neither teaches assessing the compounds in claims 12 and 13, nor comparison to a poor expansion group. However,
Buchbinder teaches (Abstract) –
The cytotoxic T-lymphocyte–associated antigen 4 (CTLA 4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non–small cell lung cancer, and other cancers
Li teaches (last paragraph of the Introduction)
In the current study, we analyzed the function of Eomes in CD8+ Tcells in a cancer model. We found the amount of Eomes was increased in exhausted CD8+ T cells in the tumor. Eomes was haplosufficient for full effector differentiation of anti-tumor CTLs and high amounts of Eomes promoted exhausted phenotypes of CD8+ TILs. Furthermore, Eomes established the transcriptional profile associated with T cell exhaustion via binding to key regulatory loci on the genome. Overall, our data have offered important insights into the mechanism whereby Eomes mediates CD8+ T cell exhaustion
Therefore, it would have been obvious to have chosen cells with low levels of the immune checkpoint proteins PD-1 and CTLA-4 in order to increase the efficacy of anti-cancer treatment. Similarly, since Eomes are associated with an increase in exhausted T cells in a tumor, it would have been obvious to use cells in which its expression is low. Furthermore, Ribas teaches the role of IFNg, and its use in conjunction with inhibitors of the checkpoint proteins PD-1 and CTLA-4 (third paragraph). In addition, Trapani teaches Granzyme B has pro-apoptotic and anti-tumor functions, implying that high expression would be beneficial in immunotherapy. Finally, Jeannin teaches that “Results show that paraformaldehyde-fixed CD86+ T cells enhance the proliferation and production of IFN-gamma by anti-CD3 mAb-stimulated naive T cells and induce proliferation of resting allogenic T cells” (Abstract).
Therefore, taken as a whole, it would have been obvious to have assessed the candidate cells for factors which would improve their therapeutic potential – namely (1) low levels of checkpoint proteins which would contribute to cancer survival and growth, (2) low levels of Eomes, which would reduce T cell exhaustion (3) high levels of IFN-g, Granzyme B and CD86, which all appear to have positive effects in controlling tumor growth.
4. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
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