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 .
Applicant filed a response to the Final Action of 5/26/2026 on 7/24/2026. Upon further consideration, the finality of the action of 5/26/2026 is withdrawn and the following is a Non-Final Action.
Applicant filed an amendment to the claims 7/24/2026. Claims 1, 9, 11, 13 are amended. Claims 2, 7, 8, 10, 15, 17, 21, 26-28 are canceled. Claims 1, 3-6, 9, 11-14, 16, 18-20, 22-25 are pending and under consideration.
Information Disclosure Statement
Applicant filed an Information Disclosure Statement (IDS) on 8/13/2026. The IDS has been considered.
Withdrawn Rejections
112a, written description: Claims 1-7, 9, 11-14, 16, 18-20, 22-25 were rejected under 112a as failing to comply with the written description requirement. Upon further consideration, the rejection is withdrawn.
New Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-6, 9, 11, 12, 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Step2A, prong 1: Is the claim directed to a law of nature, a natural phenomenon or an abstract idea?
Regarding claim 1, the claim recites a composition of “isolated hematopoietic progenitor cells (HPCs) expressing CD244 and CD48” and “stromal cells expressing CD48.” While the claim indicates that the composition is “isolated,” it is noted that the HPCs and the stromal cells are naturally occurring and function, even after isolation, as they do in nature, wherein upon contact, the cell that expresses CD48 activates the cell that expresses CD244. Thus, the composition of HPCs and stromal cells is drawn to a judicial exception (JE) of a natural product.
Claims 3, 4 are drawn to cytokines/growth factors that stimulate HPC differentiation. The cytokines/growth factors are also products of nature and function as they normally do in a body.
Claims 5, 6 are drawn to characteristics of the naturally occurring HPCs.
Claims, 9, 11, 12 are drawn to stroma that expresses/overexpresses CD48. Stroma comprises cells that are CD48 positive, such as hematopoietic cells (see Agresta et al., 2018, “The Emerging Role of CD244 Signaling in Immune Cells of the Tumor Microenvironment, “ Frontiers in Immunology, 9: 1-9 (article 2809), Figure 1).
Step2A, prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?
None of the rejected claims recite additional elements that integrate the cells into a practical application.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
Regarding claim 1 being drawn to an anti-CD244 cross-linking antibody, it is noted that the art indicates that antibody C1.7 is a mouse monoclonal antibody that targets human CD244 (see Details in Product Data Sheet from ThermoFisher Scientific (Invitrogen)). Thus, the antibody is not naturally occurring. A composition comprising HPCs and an anti-CD244 cross-linking antibody would overcome the 101 rejection.
Claim 22 is drawn to a kit that comprises at least one container. A container that holds the HPC and stromal cells does not result in something significantly more than the JE (e.g. change the cells structurally or functionally).
Claim Rejections - 35 USC § 103
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.
Claims 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Saranchova et al., 2018, “Type 2 Innate Lymphocytes Actuate Immunity Against Tumours and Limit Cancer Metastasis,” Scientific Reports, 8: 1-17 (article 2924).
Saranchova et al. teach the role of ILC2s and IL-33 in cancer development and compare the progression of the primary (TC1) or metastatic (A9) tumors with and without IL-33-gene complementation in mice transplanted with bone marrow (BM) from either wild type or mice lacking ILC2 (RORalpha -/-). RORalpha-/- BM transplanted mice are ILC2-deficient. BM chimeras were generated by reconstituting lethally irradiated B6.Pep3b mice with whole BM cells from either 4-week WT or RORalpha-/- mice. Chimeric mice with WT BM produced WT levels of ILC2 and chimeric mice transplanted with RORalpha-/- BM produced miniscule number of ILC2 (resulting from the B6.Pep3b host background). A9, A9+IL-33, or TCI cells were injected into the chimeric mice. Mice that produced ILC2s exhibited reduced tumor growth over time (Saranchova et al., Figure 4). The frequency of ILC2s isolated from lymph nodes from WT animals bearing IL-33-expressing tumors (TC-1 or A9+IL-33) was significantly increased over animals bearing tumors not expressing IL-33 (A9 alone). The frequency of ILC2s isolated from lymph nodes of mice transplanted with RORalpa-/- BM bearing IL-33 expressing tumors was less than 0.05% of total cells isolated (Saranchova et al., page 3 under Demonstration that ILC2 aid in immune recognition of cancer in vivo).
While Saranchova et al. teach transplantation of bone marrow, they do not teach transplantation of ILC2 cells. However, it would have been obvious for an artisan to transplant ILC2 cells because Saranchova et al. teach that ILC2 cells reduce the size of tumors. One would have been motivated to use ILC2 cells as an alternative to bone marrow because ILC2 cells is a cell population in bone marrow that reduces tumor cells.
It is noted that while claim 23 indicates that the ILC2 cells are obtained by the method recited in claim 13, as far as can be told, the ILC2 cells made by the method in claim 13 are the same ILC2 cells taught by Saranchova et al.
Closest Prior Art
Closest prior art for claims 13, 14, 16, 18-20:
Tiu et al., 2006, “Differential Expression of SLAM Family Receptor Markers in Normal Hematopoietic Stem Cells and Their Malignant Counterpart in MDS and AML,” Blood, 108: 1897, teach that leukemia cell line KG-1 exhibited increased expression of CD48 and CD244. Tiu et al. might be readable on claim 1 for its expression of CD48 and CD244. However, if the goal of the invention is to increase cell number (e.g. see claim 13), one would not necessarily expand a cancer cell, particularly if the context is to use the expanded cell in therapy (e.g. see claim 23).
Claim 1 requires that the HCP express CD244 and CD48 and that the composition also comprises CD244 agonist. Claus et al. 2016, Modulation of natural killer cell functions by interactions between 2B4 and CD48 in cis and in trans,” Open Biol., 6: 11 pages, teach that co-expressed CD244 (2B4) and CD48 can interact in cis. Cis interaction reduces the ability of CD244 (2B4) to bind to CD48 in trans. Subsequently, stimulation-dependent phosphorylation of CD244 (2B4) upon binding to CD48 positive target cells is reduced. Interference with the cis interaction enhanced lysis of CD48-expressing tumor cells (Claus et al., abstract). To demonstrate that cis CD244 (2B4)-CD48 interaction interfered with the trans interaction of soluble CD48, Claus et al. treated cis-CD244 (2B4)-CD48 cells with phosphatidylinositol-specific phospholipase C (PI-PLC) to remove CD48 and all other GPI-anchored proteins from the cell surface. The removal of CD48 allowed the interaction of sCD48 with CD244 (2B4) on the cell surface (Claus et al., page 2, 1st col., 1st parag. under Results and Figure 1). As this teaching applies to Tiu et al., if an artisan used KG-1, which is indicated to have increased levels of CD244 and CD48, one would not be able to treat KG-1 with a CD244 agonist as CD244 and CD48 on KG-1 would be interacting in cis with each other.
To also illustrate the point that the claims do not encompass the use of cancer cells that co-express CD244 and CD48, Agresta et al., 2018, “The Emerging Role of CD244 Signaling in Immune Cells of the Tumor Microenvironment,” Frontiers in Immunology, 9: 1-9 (article 2809), teach that high levels of CD244 propagates an inhibitory signal (e.g. see Agresta et al., Figures 2 and 3). While Agresta et al. teach the effect that increased levels of expression CD244 has on differentiated immune cells, there is no guidance on the relationship between CD244 levels and progenitor ICL2 cells.
Conclusion
Claims 13, 14, 16, 18-20 allowed.
Claims 1, 3-6, 9, 11-12 and 22-25 are rejected.
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/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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