DETAILED ACTION
Applicant’s arguments in the response filed 8/21/2026 are acknowledged and entered into the record.
Accordingly Claims 33, 35-44 have been previously withdrawn. Claims 45, 47-55 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
New Grounds of Rejection
(based on reconsideration)
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.
Claim(s) 45, 47-55 are rejected under 35 U.S.C. 103 as being unpatentable over Stroncek et al. (Chimeric Antigen Receptor T-cell Therapies for Cancer, Chapter 3 – CAR T-Cell: Cell Processing Laboratory Considerations, 2020) in view of Weinstein et al. (PgPub US2019/0240293).
Stroncek et al. teach “An important goal for manufacturing all cell therapies is to consistently produce high-quality products. This is especially true for CAR T-cells. Factors that can cause or contribute to manufacturing failure include inability to collect sufficient quantities of T-cells, microbial contamination, low levels of T-cell transduction, insufficient expansion of T-cells in culture, and low levels of CD3þ T-cells in the final CAR T-cell product.” Stroncek et al. disclose in the chart on page. 20 the steps involved in successfully manufacturing CAR-T cells including T-cell enrichment and expansion where the T-cells are placed in culture with factors that stimulate T-cell growth, followed by cell harvesting and washing. Stroncek et al. teach “the CAR-T cells must be washed to remove culture media and factors used as media supplements, such as cytokines and antibodies. Culture media, in general, are not meant to be given intravenously, and the cytokines used as culture media supplements may be toxic if given intravenously.” Stroncek et al. does not teach using serotonin receptor agonists or specific prodrug of said serotonin receptor agonist to stimulate CAR-T cells. This deficiency is made up for by Weinstein et al.
Weinstein et al. (PgPub US2019/0240293) teach “the discovery that modulation of neurological signaling pathways can modulate an immune response and, e.g., can be used to modulate an anti-cancer immune response. Accordingly, therapeutic and pharmaceutical compositions (as well as veterinary compositions) comprising neuromodulating agents and related methods are disclosed herein for treatment of cancer. The invention also features methods of modulating an immune response or immune cell activities in a subject or in isolated immune cells” (see paragraph [0002]). Weinstein et al. disclose immune cells to include but are not limited to T lymphocytes (T cells), B lymphocytes (B cells), natural killer (NK) cells, macrophages, eosinophils, mast cells, dendritic cells and neutrophils. Weinstein et al. disclose neuromodulating agents can be divided into four major categories listed in several tables, in particular Weinstein et al. disclose the neuromodulating agent is a dopamine agonist listed in Tables 2A-2L. Table 2G lists serotonin agonists including pergolide, tryptamines, lysergamides, and phenethylamines and others listed in instant claim 50. Weinstein et al. teach examples of culturing immune cells to identify agents which stimulate activation and disclose “during the culture, the agent of interest identified as described in Example 1 or Example 2 is administered at various concentrations to the cells in culture” (see paragraph [0394] example 3 and Fig. 3). Weinstein et al. found that dopamine agonists stimulate T cells and induce an increase in the production of the pro-survival cytokine IL-2 and proliferation (see also claims 57-59 of Weinstein). Weinstein et al. further disclose “A neuromodulating agent described herein can be administered to a cell in vitro (e.g., an immune cell), which can subsequently be administered to a subject (e.g., a human subject or animal model). The neuromodulating agent can be administered to the cell to effect an immune response (e.g., activation, polarization, antigen presentation, cytokine production, migration, proliferation, or differentiation) as described herein. Once the immune response is elicited, the cell can be administered to a subject (e.g., injected) (see paragraph [0233]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of CAR T-cell manufacturing taught by Stroncek et al. using the neuromodulating agents taught by Weinstein et al. to stimulate and induce proliferation of T-cells. One of ordinary skill in the art would have been motivated to do so because Stroncek et al. teach proliferation and expansion is a critical step in successful manufacturing of therapeutic CAR T-cells and Weinstein et al. teach agents that have been shown to stimulate and induce proliferation of T-cells. One of skill in the art, based on the teachings would know to wash the stimulated T-cells to remove the neuromodulating agents, as taught by Stroncek et al. before administration to a subject. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to use the neuromodulating agents, such as dopamine agonists, taught by Weinstein et al. to induce proliferation and expansion of healthy T-cells in the manufacturing of therapeutic CAR T-cells as taught by Stroncek et al. to make the claimed composition.
Response to Arguments
Applicant's argue in the response filed 8/21/2026 that Weinstein is primarily directed to a method of treating a subject by administering a neuromodulating agent and that all of the claims require administering the neuromodulating agent. Applicants do acknowledge that Weinstein does mention cell-based therapies at paragraphs [0232]-[0235]. Applicants additionally point to unexpected results established in Examples 1 and 3 of the present application. It is noted that the instant specification does not provide any in vivo data of a subject being administered the claimed composition, furthermore, Examples 1 and 3 only provides data of the specific agonist “pergolide mesylate” and none of the other long list of serotonin receptor agonists claimed. These arguments have been considered and the new 103(a) obviousness rejection has been set forth above.
All previous rejections set forth in the office action mailed 5/21/2026 are hereby withdrawn.
Conclusion
Claims 45, 47-55 are rejected.
No Claim is allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643
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