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 .
Status of the Claims
Applicant’s submission filed 04 November 2025 has been entered. Claims 1-6, 8-18, 20-21, 23-25, 27, 29, and 31-37 are pending. Claims 1-4, 6, 8, 10, 12, 25, 29, 34, and 36 have been amended, while claims 7 and 26 have been cancelled without prejudice or disclaimer. Therefore, prosecution on the merits continues for claims 1-6, 8-11, 25, 27, and 29 as being drawn to the elected invention, with claims 12-18, 20-21, 23-24, and 31-37 withdrawn for reading on the non-elected inventions. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to the Specification
The substitute Specification filed 04 November 2025 is acknowledged and entered into the application file. With that, Applicant’s amendments to Paragraph [000250] removing the browser-executable code obviates the objection of record.
Therefore, the objection is withdrawn.
RE: IDS size fee and assertion
The Examiner acknowledges that the IDS Size Fee Assertion for the IDS filed 25 June 2025 was made within the Transmittal Letter filed 25 June 2025.
Therefore, the IDS filed 25 June 2025 has been considered.
RE: Objections to claims 1, 4, 10, and 25
Applicant’s amendments to each of claims 1, 4, 10, and 25 correct the minor informalities and obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 1-11, 25-27, and 29 under 35 USC 112(a)
The cancellation of claims 7 and 26 renders the rejection moot for those claims. For the remaining claims, Applicant’s amendments to each of independent claims 1 and 25 removing the “derivative or an analogue thereof” language obviates the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 3-5, 25-27, and 29 under 35 USC 112(b) The cancellation of claim 26 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendment to claims 3, 4, and 25 correct the scope of each claim and obviate the rejections of record.
Therefore, the rejections are withdrawn.
RE: Rejection of claims 1-4, 6-7, 9-11, 25-27, and 29 under 35 USC 102(a)(1) and 35 USC 102(a)(2) over Rosen et al
The cancellation of claims 7 and 26 renders the rejection moot for those claims. For the remaining claims, Applicant’s amendments to each of independent claims 1 and 25 requiring the immune cell to be cryopreserved after it is subjected to the small compound treatment obviates the rejection of record. It is of note that these are considered new limitations, as the scope of previous claims 7 and 26 did not necessarily require the cryopreservation step to be after the small compound treatment and was thus broader than what is currently recited.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1 and 6-10 under 35 USC 102(a)(2) over Ports et al
The cancellation of claim 7 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendments to independent claim 1 requiring the immune cell to be cryopreserved after it is subjected to the small compound treatment obviates the rejection of record. It is of note that this is considered a new limitation, as the scope of previous claim 7 did not necessarily require the cryopreservation step to be after the small compound treatment and was thus broader than what is currently recited.
Therefore, the rejection is withdrawn.
However, Applicant’s amendments are addressed in so far as they are applicable to the claims as amended within a new ground of rejection under 35 USC 103:
Applicant has traversed the rejection, asserting in Pages 22-23 of the Remarks filed 04 November 2025 that Ports et al fail to even suggest the treatment of immune cells with the recited small molecule compounds prior to cryopreservation. In response, the Examiner respectfully submits that Ports et al disclose that the immune cells can be isolated, incubated, and/or engineered before being cryopreserved. See, for example, Paragraph [0515]. With that, Ports et al further disclose that the immune cells can be incubated or cultured in the presence of lenalidomide during the engineering step, wherein the lenalidomide treatment increases the proliferation or expansion of cells (Paragraph [0539]). Therefore, the ordinary artisan would recognize that Ports et al reasonably suggests the culture of immune cells with lenalidomide prior to the cryopreservation step.
Applicant has further traversed the rejection, asserting in Pages 24-25 of the Remarks filed 04 November 2025 that the treatment of immune cells with the recited small compounds prior to cryopreservation resulted in several beneficial effects, including an improved antigen specific recognition, cytotoxic effect, efficacy, and persistency. Applicant cites Examples 2-3 and Figures 8A-B, 9A-B for support. In response, the Examiner respectfully submits that the features upon which Applicant relies (i.e., an improved antigen specific recognition, efficacy, and persistency) are not recited in the rejected claims. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). With that, the Examiner notes that the disclosure of Ports et al reasonably suggests that immune cells will have an enhanced cytotoxic effect following lenalidomide treatment. See Paragraphs [0636]-[0638], [0640], [0645]-[0647] and Figures 1, 4 of Ports et al. Therefore, the ordinary artisan would be readily apprised of the asserted beneficial effect as recited in the instant claims.
The Examiner further notes that the cited results are not commensurate in scope with at least independent claims 1 and 25, as Examples 2-3 of the instant disclosure are respectively directed to iNK or iT cells each expressing a CAR specific for CD19. Therefore, the scope of the instant claims is much broader than the supporting examples.
RE: Rejection of claims 1-10, 25-27, and 29 under 35 USC 103 over Ports et al in view of Valamehr et al
The cancellation of claims 7 and 26 renders the rejection moot for those claims. For the remaining claims, Applicant’s amendments to each of independent claims 1 and 25 requiring the immune cell to be cryopreserved after it is subjected to the small compound treatment obviates the rejection of record. It is of note that these are considered new limitations, as the scope of previous claims 7 and 26 did not necessarily require the cryopreservation step to be after the small compound treatment and was thus broader than what is currently recited.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as amended:
Applicant has traversed the rejection, asserting in Pages 23-24 of the Remarks filed 04 November 2025 that Valamehr et al fail to disclose the culture of immune cells with the presently claimed small compounds during in vitro expansion followed by cryopreservation. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Valamehr et al is a secondary reference relied upon to teach the differentiation of iPSCs into T cells.
RE: Rejection of claims 1 and 6-11 under 35 USC 103 over Ports et al in view of Morgan et al
The cancellation of claim 7 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendments to independent claim 1 requiring the immune cell to be cryopreserved after it is subjected to the small compound treatment obviates the rejection of record. It is of note that this is considered a new limitation, as the scope of previous claim 7 did not necessarily require the cryopreservation step to be after the small compound treatment and was thus broader than what is currently recited.
Therefore, the rejection is withdrawn.
However, Applicant’s remarks are addressed in so far as they are applicable to the claims as amended:
Applicant has traversed the rejection, asserting in Pages 23-24 of the Remarks filed 04 November 2025 that Morgan et al fail to disclose the culture of immune cells with the presently claimed small compounds during in vitro expansion followed by cryopreservation. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Morgan et al is a secondary reference relied upon to teach the treatment of the immune cells with about 10 nM to about 20 μM of dexamethasone.
RE: Rejection of claims 1-11, 25-27, and 29 over claims 1-2, 5-6, 17, 21-22, and 26 of US Patent 12,281,329 B2 in view of Ports et al and Morgan et al
The cancellation of claims 7 and 26 renders the rejection moot for those claims. For the remaining claims, Applicant’s amendments to each of independent claims 1 and 25 requiring the immune cell to be cryopreserved after it is subjected to the small compound treatment obviates the rejection of record. It is of note that these are considered new limitations, as the scope of previous claims 7 and 26 did not necessarily require the cryopreservation step to be after the small compound treatment and was thus broader than what is currently recited.
Therefore, the rejection is maintained and amended to encompass the claims as written.
New/Maintained Grounds of Rejection
Claim Interpretation
Under the broadest reasonable interpretation of instant claims 10 and 27, all of the “optional” limitations are not required.
Furthermore, Applicant has defined “substantially free” – as seen in instant claim 8 – as a composition that is free of a specified substance or its source thereof, such as, 95% free, 96% free, 97% free, 98% free, 99% free of the specified substance or its source thereof, or is undetectable as measured by conventional means. See Paragraph [00044] of the Specification filed 03 June 2022.
In regards to instant claims 3, 25, and 27, Applicant lists a representative number of species of “CD16 variants” within Paragraphs [000105]-[000106] of the instant Specification filed 03 June 2022, along with an associated structure-function relationship. More specifically, Applicant has listed different species of "high affinity CD16”, "non-cleavable CD16", or "high affinity non-cleavable CD16 (hnCD16)," CD16 variants, which refer to a natural or non-natural variants of CD16. With that, Applicant explains that the wildtype CD16 has low affinity and is subject to ectodomain shedding, a proteolytic cleavage process that regulates the cell's surface density of various cell surface molecules on leukocytes upon NK cell activation. F176V and F158V (without signal peptide) are exemplary natural CD16 polymorphic variants having high affinity. A CD16 variant having the cleavage site (position 195-198) in the membrane-proximal region 29 (position 189-212) altered or eliminated is not subject to shedding. Applicant notes that the cleavage site and the membrane-proximal region are described in detail in International Pub. No. WO 2015/148926, which is incorporated by reference. The CD16 S197P variant is an engineered non-cleavable version of CD16. A CD16 variant comprising both F158V and S197P has high affinity and is non-cleavable. Another exemplary high affinity and non-cleavable CD16 (hnCD16) variant is an engineered CD16 comprising an ectodomain originated from one or more of the 3 exons of the CD64 ectodomain.
Likewise, in regards to instant claims 3, 5, and 25, Applicant lists a representative number of species of “antibody fragments” within Paragraph [00132] of the instant Specification filed 03 June 2022, along with an associated structure-function relationship. More specifically, Applicant discloses that “[n]on-limiting examples of antibody fragments include Fab, Fab', F(ab)'2, F(ab)'3, Fv, antigen binding single chain variable fragment (scFv), (scFv)2, disulfide stabilized Fv (dsFv), minibody, diabody, triabody, tetrabody, single- domain antigen binding fragments (sdAb, Nanobody), recombinant heavy-chain-only antibody (VHH), and other antibody fragments that maintain the binding specificity of the whole antibody.”
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.
Claims 1, 6, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable by Ports et al (WO 2018/204427 A1, of record on IDS filed 25 June 2025).
Ports et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 1: Ports et al disclose methods, compositions, and uses involving immunotherapies and an immunomodulatory compound (Abstract).
As such, Ports et al disclose the culturing of ex vivo T cells in the presence of a lenalidomide immunomodulatory compound and formulating the lenalidomide-treated cells in the presence of a cryoprotectant prior to being cryopreserved, wherein the lenalidomide treatment increases the proliferation or expansion of the T cells (Paragraphs [0027]-[0029], [0046]-[0047], [0076], [0475], [0515], [0539]).
Ports et al further disclose that T cells that have been thawed and treated with lenalidomide have an enhanced cytolytic activity compared to untreated T cells (Paragraphs [0636]-[0638], [0640], [0645]-[0647] Figures 1, 4).
However, Ports et al do not exemplify or reduce to practice a method of treating expanding ex vivo T cells with lenalidomide and subsequently cryopreserving the lenalidomide-treated T cells, wherein the lenalidomide treatment enhances the post-thaw cytolytic activity of the T cells, as required by instant claim 1.
Therefore, it would have been prima facie obvious to have modified the method of Ports et al such that the T cells are treated with lenalidomide prior to being cryopreserved. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to treat the T cells with lenalidomide prior to cryopreservation, as Ports et al disclose that the beneficial effects of lenalidomide within the T cells are delayed about 50 hours post-treatment (Paragraph [0638]). Accordingly, the ordinary artisan would have recognized the potential in treating the T cells with lenalidomide, allowing the incubation of the treatment for about two days, and then cryopreserving the lenalidomide-treated T cells such that there is a limited delay in the beneficial effects post-thaw. The ordinary artisan also would have had a reasonable expectation of success given that Ports et al disclose protocols for treating, cryopreserving, and thawing the ex vivo T cells. See MPEP § 2143(I)(G).
Consequently, Ports et al render obvious a method wherein expanding ex vivo T cells are treated with lenalidomide and subsequently cryopreserved, wherein the lenalidomide treatment enhances the post-thaw cytolytic activity of the T cells. This therefore renders obvious the method of the instant claim.
Regarding claim 6: Following the discussion of claim 1, Ports et al further disclose the repeated stimulation of T cells with lenalidomide (Paragraphs [0646]-[0647]; Figures 4A-B). Therefore, it would have been prima facie obvious to have restimulated the lenalidomide-treated cryopreserved cells with lenalidomide post-thaw. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to restimulate the cryopreserved cells, as it was found that repeated lenalidomide treatments enhanced the expansion of the T cells (Paragraph [0647]), and would have had a reasonable expectation of success given the protocols outlined in Ports et al. See MPEP § 2143(I)(G). This therefore renders obvious the method of the instant claim.
Regarding claim 8: Following the discussion of claim 1, Ports et al further disclose that the lenalidomide-treated T cells are washed and then suspended in a freezing solution, wherein the freezing solution is comprised of PBS containing 20% DMSO and 8% human serum albumin (Paragraphs [0515], [0539]). As the cells are washed and re-suspended in freezing solution that does not comprise lenalidomide, the cryopreservation does not comprise lenalidomide. This therefore reads on the method of the instant claim.
Regarding claim 9: Following the discussion of claim 1, Ports et al further disclose that lenalidomide-treated T cells have an enhanced efficacy and ability in tumor control in vivo when compared to untreated T cells (Paragraphs [0653]-[0656]; Figure 7). This therefore reads on the method of the instant claim.
Regarding claim 10: Following the discussion of claim 1, Ports et al further disclose that the T cells are treated with lenalidomide and concurrently stimulated with IL-2, IL-15 and/or IL-7 (Paragraphs [0516], [0518], [0538]-[0539]). As the stimulation can comprise one of IL-2, IL-15, or IL-7, and is thereby essentially free of the two remaining cytokines, this therefore reads on parts (ii) or (iii) of the method of the instant claim.
Claims 1-6, 8-10, 25, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Ports et al (WO 2018/204427 A1, of record on IDS filed 25 June 2025) in view of Valamehr et al (WO 2017/078807 A1, of record on IDS filed 05 December 2022).
The discussion of Ports et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Ports et al render obvious claims 1, 6, and 8-10. Valamehr et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 11 May 2017.
Regarding claims 2-3, 25, 27, and 29: As aforementioned in the discussion of claim 1 above, Ports et al render obvious a method wherein expanding ex vivo T cells are treated with lenalidomide and subsequently cryopreserved, wherein the lenalidomide treatment enhances the post-thaw cytolytic activity of the T cells.
Ports et al further disclose that the ex vivo T cells are transfected with a polynucleotide encoding a chimeric antigen receptor (CAR) that contains an extracellular antigen-recognition domain that specifically binds to an antigen, including BCMA or CD19 (Paragraphs [0236]-[0237], [0247]-[0248], [0376]-[0425]).
Ports et al do not disclose that the T cells are differentiated from an induced pluripotent stem cell (iPSC), as required by instant claims 2 and 25.
Valamehr et al, however, disclose culture platforms, cell media, and methods of differentiating pluripotent cells into hematopoietic cells (Abstract). As such, Valamehr et al disclose iPSC-derived T cells comprising a CAR specific for CD19, wherein the iPSC is genetically modified to comprise the CAR and then differentiated into the T cell (Paragraphs [0003], [00017], [00021], [00041], [00043]-[00046], [00052], [00062], [000163], [000258]-[000261], [000278], [000380]-[000381]; Figures 24, 38).
Therefore, it would have been prima facie obvious to have substituted the CAR-T cells of Ports et al for the iPSC-derived CAR-T cells of Valamehr et al, as doing so would have been a simple substitution of one CAR-T cell for another. See MPEP § 2143(I)(B). One of ordinary skill before the effective filing date of the invention would have recognized that the CAR-T cells are functionally comparable, as the T cells differentiated from iPSCs retain the CAR expression (Valamehr et al: Paragraphs [000380]-[000381]), and thereby would have been able to substitute the CAR-T cells with predictable results.
Consequently, Ports et al as modified by Valamehr et al render obvious a method of enhancing post-thaw cytotoxicity, wherein iPSC-derived T cells (claims 2, 29) comprising a polynucleotide encoding a CAR that contains an extracellular antigen-recognition domain that specifically binds to an antigen (claims 3, 27) are treated with lenalidomide and subsequently cryopreserved, wherein the lenalidomide treatment enhances the post-thaw cytolytic activity of the CAR-T cells. This therefore renders obvious the method of instant claim 25.
Regarding claim 4: Following the discussion of claim 3, Ports et al further disclose that the CAR contains an extracellular antigen-recognition domain that specifically binds to BCMA or CD19 (Paragraphs [0058], [0376]-[0425]). This therefore reads on the method of the instant claim.
Regrading claim 5: Following the discussion of claim 3, Ports et al further disclose that the CAR can be a multispecific CAR comprising antigen binding domains for bispecific antibodies, multispecific single-chain antibodies, e.g., diabodies, triabodies, and tetrabodies, tandem di-scFvs, and tandem tri-scFvs (Paragraphs [0057]-[0058], [0098], [0116], [0224], [0240], [0379]-[0383]). As the polynucleotide encoding the CAR will co-express the antibody scFv fragments of the tandem di-scFvs, for example, this therefore reads on the method of the instant claim.
Claims 1, 6, and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Ports et al (WO 2018/204427 A1, of record on IDS filed 25 June 2025) in view of Morgan et al (Front Immunol, 2017, of record).
The discussion of Ports et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Ports et al render obvious claims 1, 6, and 8-10. Morgan et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 11: As aforementioned in the discussion of claim 1 above, Ports et al render obvious a method wherein expanding ex vivo T cells are treated with lenalidomide and subsequently cryopreserved, wherein the lenalidomide treatment enhances the post-thaw cytolytic activity of the T cells.
Ports et al further disclose that the lenalidomide is administered at a concentration of 1 μM (Paragraphs [0133], [0642], [0645]; Figure 3F).
Ports et al further disclose that, in some embodiments of the invention, the ex vivo cells can instead by natural killer (K) cells (Paragraphs [0234], [0475], [0477]). Ports et al further disclose that the cells may be stimulated with agents including IL-2 (Paragraph [0518]).
Ports et al do not disclose that the cells are treated with dexamethasone at a concentration of about 10 nM to about 20 μM, as required by instant claim 11.
Morgan et al, however, disclose that 100 nM of dexamethasone enhances the proliferation and survival of primary natural killer cells (pNK) stimulated with IL-2 and IL-12 (Abstract; Page 2, Column 1; Page 2, Cytokine Stimulation of pNK Cells; Pages 4-5, Dexamethasone Augments…; Figures 1H,I).
Therefore, it would have been prima facie obvious to have modified the method of Ports et al such that the ex vivo natural killer cells are instead treated with 100 nM dexamethasone. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to treat the natural killer cells with an agent that enhances the proliferation and survival of the cells, and would have had a reasonable expectation of success since Ports et al disclose that the enhanced cytolytic capabilities of the cells are due to the promotion of continued function and/or survival of the cells after initial activation (Paragraph [0638]). Accordingly, the ordinary artisan would have recognized that the pNK cells treated with dexamethasone and stimulated with IL-2 and IL-12 of Morgan et al would have also had an enhanced cytolytic capability, as evidenced by their enhanced survival. See MPEP § 2143(I)(G).
Consequently, Ports et al as modified by Morgan et al render obvious a method of increasing the post-thaw cytotoxicity of NK cells, wherein NK cells are treated with 100 nM dexamethasone and stimulated. As 100 nM dexamethasone falls within the claimed range of about 10 nM to about 20 μM, this therefore renders obvious the method of the instant claim. See MPEP § 2131.03.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6, 8-11, 25, 27, and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-6, 17, 21-22, and 26 of U.S. Patent No. 12,281,329 B2 in view of Ports et al (WO 2018/204427 A1, of record on IDS filed 25 June 2025) and Morgan et al (Front Immunol, 2017, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims. More specifically, the patented claims are not identical because no single patented claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patent claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a composition comprising immune cells, and at least one agent, wherein: (a) the immune cells comprise a population of modulated immune cells that are modulated by the at least one agent; (b) the population of modulated immune cells have improved therapeutic potential in comparison to unmodulated immune cells that are not modulated by the at least one agent; (c) the at least one agent comprises a GSK3 Inhibitor; (d) the immune cells are genetically modified to comprise an insertion, a deletion, or a nucleic acid replacement; and (e) the modulated immune cells comprise NK cells.
Patent claim 2 further limits the composition of patent claim 1, wherein the population of modulated immune cells comprises cells that have: i) improved proliferation, cytotoxicity, cytokine response, cytokine release, cell recall, and/or persistence; ii) improved cell expansion, maintenance, differentiation, dedifferentiation, and/or survival rate; and/or iii) increased number or ratio of one or more desired subpopulations of immune cells, in comparison to immune cells not contacted with said at least one agent
Patent claims 21-22 and 26 further limit the composition of patent claim 1, wherein the population further comprises immunomodulatory drugs (IMiDs), including lenalidomide.
The combination of patent claims 1-2, 21-22, and 26 do not teach that immune cells have an enhanced post-thaw cytotoxicity, nor that the immune cells are treated with the agent during in vitro expansion of the immune cell and are subsequently cryopreserved.
Ports et al, however, teach that expanding ex vivo T cells are treated with lenalidomide and subsequently cryopreserved, wherein the lenalidomide treatment enhances the post-thaw cytolytic activity of the T cells (Paragraphs [0027]-[0029], [0046]-[0047], [0076], [0475], [0515], [0539], [0636]-[0638], [0640], [0645]-[0647]; Figures 1, 4).
Therefore, it would have been prima facie obvious to have modified the lenalidomide-treated immune cell population of the patented claims to have been treated with the lenalidomide agent during the in vitro expansion of the immune cells and subsequently cryopreserved such that the immune cells have an enhanced post-thaw cytotoxicity, as detailed in Ports et al. One of ordinary skill in the art would have been motivated to generate immune cells that can undergo long-term storage via cryopreservation yet still have enhanced cytotoxic capabilities, and would have had a reasonable expectation of success based on the disclosure of Ports et al.
Consequently, patent claims 1-2, 21-22, and 26 in view of Ports et al render obvious a method of enhancing post-thaw cytotoxicity in a cell, wherein an immune cell is subjected to treatment with lenalidomide during the in vitro expansion of the immune cell, and is subsequently cryopreserved. This therefore renders obvious the method of instant claim 1.
Patent claims 5-6 further limit the composition of patent claim 1, wherein the immune cell is differentiated from an induced pluripotent stem cell into a NK cell. This therefore renders obvious the method of instant claims 2, 25, and 29 when considering the method of patent claim 1.
Patent claim 17 further limits the composition of patent claim 1, wherein the immune cell is genetically modified to comprise introduced expression of HLA-G. This therefore reads on the method of instant claim 3.
With that, instant claims 4-6, 8-11 and 27 are known from the prior art and can be further incorporated into the method rendered obvious by patent claims 1-2, 21-22, and 26:
Ports et al further teach the limitations recited in instant claims 4-6, 8-10, and 27.
Morgan et al further teach the limitation recited in instant claim 11.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633