DETAILED ACTION
Applicant's submission filed on May 26, 2026 has been entered. Any prior rejection that is not repeated or addressed below is either moot or withdrawn in view of Applicant’s amendment.
The rejection of claims 1, 2, 6, 27, 28, 32, 35, 40, 67 and 76 under 35 U.S.C. 102(a)(1) as anticipated by Sharei et al. (WO 2016/070136 A1) is withdrawn in view of Applicant’s persuasive argument concerning the teachings of Sharei being limited to the constriction width of 3.5 microns for naïve T and naïve B cells (see page 10 of Applicant’s remarks filed May 26, 2026). Upon review of the specification, there is no teaching or fair suggestion to apply a constriction width of about 3.5 microns (to the exclusion of about 4.0 microns and about 4.5 microns) to PMBCs including each of T cells, B cells, NK cells and monocytes.
For the same reasons, the obviousness type double patenting rejections of record that relied on Sharei et al. (WO 2016/070136 A1), as well as the provisional rejections that relied on Sharei et al. (WO 2016/070136 A1) are all withdrawn.
Claims Summary
Claims 1, 2, 6, 27, 28, 32, 35 and 40
Claim 1 is directed to a plurality of modified PBMCs comprising an exogenous antigen intracellularly, formed by passing a cell suspension of isolated input PMBCs comprising T cells, B cells, NK cells and monocytes through a cell-deforming constriction having a width of about 3.5 microns to deliver the antigen into each of the T cells, B cells, NK cells and monocytes. The plurality of modified PBMCs exhibit improved delivery of the antigen into the cells as compared to corresponding modified PBMCs passed through a cell-deforming constriction having a width from about 4.0 microns, or about 4.5 microns. The percentage of cells receiving the antigen is as follows:
Between about 70% and about 85% of the T cells – support for both percentages is found in paragraph [0208] of the published application US 2024/0132839
Between about 50% and about 65% of the B cells – support for both percentages is found in the combined teachings of paragraph [0208] of the published application US 2024/0132839, and Figure 12B (bar graph labeled “CD20+ 3 kDa Delivery”, see the bar labeled “10-3.5”)
Between about 55% and about 70% of the NK cells - support for “about 70%” is found in the combined paragraph [0208] of the published application US 2024/0132839, and Figure 12B (bar graph labeled “CD56+ 3 kDa Delivery”, see the bar labeled “10-3.5”); support for the lower percentage of “about 55%” is inherently disclosed in the bar graph that shows 70% (i.e., the bar is filled from 1-70%, which includes “about 55%”)
Between about 80% and about 90% of the monocytes - support for both percentages is found in the combined teachings of paragraph [0208] of the published application US 2024/0132839, and Figure 12A (bar graph labeled “CD14+ 3 kDa Delivery”, see the bar labeled “10-3.5”)
Claim 40 is directed to a composition thereof. The antigen comprises a cancer antigen, an infectious disease antigen, or a viral-disease associated antigen (claim 2). The plurality of modified PBMCs further comprises an adjuvant (claim 6). The antigen and/or adjuvant is present in at least about 70% of the cells in the plurality of PBMCs (claim 27). The adjuvant is, for example, CpG ODN, among others (claim 28). The modified PBMCs have increased expression of one or more one or more cytokines (e.g., IFN-α (claim 35)) as compared to corresponding modified PBMCs passed through a cell-deforming constriction having a width from about 4.0 microns, or about 4.5 microns.
Claims 48, 61, 62 and 96
Claim 48 is directed to a method for stimulating an immune response in an individual in need thereof, comprising:
Passing a plurality of PBMCs through a cell deforming constriction having a width of 3.5 microns, thereby causing perturbations of the PBMCs such that an antigen in contact therewith enters the PBMCs;
Incubating the plurality of PBMCs comprising the antigen with a conditioning agent for about 4, 4.5 hours, etc. or 24 hours, thus generating a conditioned plurality of PBMCs comprising the antigen;
Administering the conditioned plurality of PBMCs comprising the antigen to the individual; administration is prior to, concurrently with, or following administration of a cytokine, an immune checkpoint inhibitor, a therapeutic agent, or a combination thereof (claim 61); the cytokine is IL-15, the immune checkpoint inhibitor is targeted to PD-1, for example, and the therapeutic agent is a chemotherapeutic agent (claim 62).
The conditioned PBMCs exhibit one or more improved properties compared to a corresponding non-conditioned PBMCs passed through a cell-deforming constriction having a width of about 4.0 microns, or about 4.5 microns. The improved properties comprise improved delivery of the antigen per cell of the input PBMCs and/or improved antigen-specific response. The conditioning agent comprises a CpG ODN, for example (claim 96).
Claims 67, 69, 71, 76 and 97
Claim 67 is directed to a method of producing a plurality of PBMCs, comprising passing an isolated plurality of PBMCs comprising T cells, B cells, NK cells and monocytes through a cell deforming constriction having a width of about 3.5 microns, thereby causing perturbations of the PBMCs such that an antigen enters each of the T cells, B cells, NK cells and monocytes. The conditioned plurality of PBMCs exhibit improved delivery of the antigen into each of the T cells, B cells, NK cells and monocytes compared to a corresponding plurality of PBMCs passed through a cell-deforming constriction having a width of about 4.0 microns, or about 4.5 microns. The percentage of cells receiving the antigen is as follows:
Between about 70% and about 85% of the T cells
Between about 50% and about 65% of the B cells
Between about 55% and about 70% of the NK cells
Between about 80% and about 90% of the monocytes
The method further comprises incubating a plurality of PBMCs with a conditioning agent for about 4 to about 24 hours (claim 97). The plurality of PBMCs are passed through the cell-deforming constriction before being conditioned (claim 69). The conditioning agent comprises a CpG ODN, for example (claim 71). In another embodiment, the plurality of PMBCs is incubated with an agent that enhances the viability and/or function of the PBMCs as compared to corresponding PBMCs that have not been incubated with the agent (claim 76).
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 1, 2, 6, 27, 28, 32, 35, 40, 48, 61, 62, 67, 69, 71, 76, 96 and 97 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The claims recite, “improved delivery” (claims 1, 48 and 67), “one or more improved properties” (claim 48), and “improved antigen-specific response” (claim 48), and combinations thereof. This language does not appear to be disclosed in the claims or specification as originally filed. All dependent claims are included in this rejection.
In the remarks filed May 26, 2026, Applicant asserts that the language “improved delivery” is supported by Example 12 and Figures 12A and 12B, which show that delivery of an antigen into each of the T cells, B cells, NK cells and monocytes, shows an increase in percentage of cells receiving the antigen. Applicant argues that “one or more improved properties” (claim 48), and “improved antigen-specific response” (claim 48) is supported in Examples 12-14, and Figures 12A, 12B, 13 and 14.
In response, showing an increase in the percentage of cells receiving the antigen is not commensurate in scope with a stated conclusion at the time of filing that the results are “improved delivery”. Similarly, showing an increase in an antigen-specific response and an increase in cytokine production is not commensurate in scope with a conclusory statement at the time of filing that the results are “improved properties” or “improved antigen-specific response”.
To overcome this rejection, the following changes are suggested:
Replace “improved delivery” with “increased delivery”, or (claims 1, 48 and 67)
Replace “improved antigen-specific response” with “increased antigen-specific response” (claim 48)
Remove “improved properties” (claim 48)
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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