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 17 November 2025 has been entered. Claims 123, 125-132, and 134-144 are pending. Claims 123, 126-127, 130, 132, and 134 have been amended, while claims 115-122, 124, and 133 have been cancelled without prejudice or disclaimer and claims 135-144 have been newly added. Therefore, prosecution on the merits continues for claims 123, 125-132, and 134-144. 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 claims 117, 127, and 134
The cancellation of claim 117 renders the objection of record moot for that claim. For the remaining claims, Applicant’s amendments to each of claims 127 and 134 obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 116 and 126 under 35 USC 112(b)
The cancellation of claim 116 renders the rejection moot for that claim. For the remaining claim, Applicant’s amendment to instant claim 126 removing the recitation of “Table 1” obviates the rejection of record.
Therefore, the rejections are withdrawn.
RE: Rejection of claims 115-118, 120, and 122 under 35 USC 103 over Hadrup et al
The cancellation of each of claims 115-118, 120, and 122 renders the rejection of record moot for those claims.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 115-120 and 122 under 35 USC 103 over Hadrup et al in view of Jensen et al and Butler et al
The cancellation of each of claims 115-120 and 122 renders the rejection of record moot for those claims.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 115-118, 120-123, 125-127, and 132-134 under 35 USC 103 over Hadrup et al in view of Lobb et al
The cancellation of each of claims 115-118, 120-122, and 133 renders the rejection of record moot for those claims. For the remaining claims, Applicant has amended independent claims 123 and 144 to each require the hapten to be selected from fluorescein, urushiol, quinone, biotin, and dinitrophenol, or a derivative thereof – which was previously presented in instant claim 127 – as well as the repeated administration of the hapten antigen presenting cell to the subject – which was previously presented in cancelled claim 124. As claim 124 was not included within the rejection of record, Applicant’s amendments obviate the rejection.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 115-118, 120-127, and 132-134 under 35 USC 103 over Hadrup et al in view of Lobb et al and Rushworth et al
The cancellation of each of claims 115-118, 120-122, 124, and 133 renders the rejection of record moot for those claims. For the remaining claims, Applicant has amended independent claims 123 and 144 to each require the hapten to be selected from fluorescein, urushiol, quinone, biotin, and dinitrophenol, or a derivative thereof – which was previously presented in instant claim 127 – as well as the repeated administration of the hapten antigen presenting cell to the subject – which was previously presented in cancelled claim 124.
With that, Applicant's accompanying arguments filed 17 November 2025 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Page 7 of the Remarks filed 17 November 2025 that Hadrup et al teach non-cellular scaffolds for antigenic presentation, and that the non-cellular scaffolds are more efficient than dendritic cells in presenting antigens. In response, the Examiner respectfully submits that the ordinary artisan would have recognized that the aAPC scaffold of Hadrup et al is functionally comparable to APCs, as both are capable of expanding antigen-specific T cells. See, for example, Paragraphs [0056], [0363], and Example 14 of Hadrup et al. Therefore, even if the aAPC scaffold of Hadrup et al is more efficient than dendritic cells, the Examiner respectfully submits that the disclosure of Hadrup et al still reasonably suggests the use of dendritic cell APCs, especially since a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, even nonpreferred embodiments. See MPEP § 2123: Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989); Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
Applicant has further traversed the rejection, asserting in Pages 7-8 of the Remarks filed 17 November 2025 that the cited prior art references only teach the targeting of a single cell and fail to teach the targeting of two separate cells for the two separate CARs. In response, the Examiner respectfully submits that the features upon which Applicant relies (i.e., the targeting of two separate cells) 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). Furthermore, as the CAR-T cells of Hadrup et al as modified by Lobb et al comprise a CAR that specifically binds to a tumor antigen and a CAR that specifically binds to a hapten, the CAR-T cells will necessarily be capable of targeting two separate cells.
Applicant has further traversed the rejection, asserting in Pages 8-9 of the Remarks filed 17 November 2025 that Lobb et al fail to teach methods for expanding T cells or CAR-T cells, and thus there would not have been any reason to modify the method of Hadrup et al with Lobb et al since it would have changed the principle of operation of Hadrup et al. In response, the Examiner respectfully submits that the disclosures of both Hadrup et al and Lobb et al are concerned with the treatment of cancer via the killing of tumor cells. See, for example, Paragraphs [0134], [0330], [0341], and [0346] of Hadrup et al and Paragraphs [0029], [0073] of Lobb et al. Therefore, the principle of operation aligns for both disclosures.
Applicant has lastly traversed the rejection, asserting in Pages 9-10 of the Remarks filed 17 November 2025 that Rushworth et al relates to the restimulation of CAR-T cells in vitro, which cannot be reasonably translated to the restimulation of CAR-T cells in vivo. In response, the Examiner respectfully submits that Applicant has failed to provide substantiated evidence and/or secondary considerations as to why the ordinary artisan would not reasonably consider the results of Rushworth et al to be translatable in vivo. Accordingly, Applicant’s arguments are not persuasive, as arguments presented by Applicant cannot take the place of evidence in the record. See MPEP § 2145(I): In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.").
Therefore, the rejection over claims 123, 125-127, 132, and 134 is maintained and amended to encompass the claims as written.
RE: Rejection of claims 115-118, 120-123, 125-129, and 132-134 under 35 USC 103 over Hadrup et al in view of Lobb et al, Jensen et al, and Butler et al
The cancellation of each of claims 115-118, 120-122, and 133 renders the rejection of record moot for those claims. For the remaining claims, Applicant has amended independent claims 123 and 144 to each require the hapten to be selected from fluorescein, urushiol, quinone, biotin, and dinitrophenol, or a derivative thereof – which was previously presented in instant claim 127 – as well as the repeated administration of the hapten antigen presenting cell to the subject – which was previously presented in cancelled claim 124. As claim 124 was not included within the rejection of record, Applicant’s amendments obviate the rejection.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 115-118, 120-123, 125-127, and 130-134 under 35 USC 103 over Hadrup et al in view of Lobb et al and Schuijs et al
The cancellation of each of claims 115-118, 120-122, and 133 renders the rejection of record moot for those claims. For the remaining claims, Applicant has amended independent claims 123 and 144 to each require the hapten to be selected from fluorescein, urushiol, quinone, biotin, and dinitrophenol, or a derivative thereof – which was previously presented in instant claim 127 – as well as the repeated administration of the hapten antigen presenting cell to the subject – which was previously presented in cancelled claim 124. As claim 124 was not included within the rejection of record, Applicant’s amendments obviate the rejection.
Therefore, the rejection is withdrawn.
RE: Provisional rejection of claims 115-134 over claims 115, 120-122, 128, 135, and 140-143 of copending Application No, 17/265,484 in view of Hadrup et al and Rushworth et al
The cancellation of each of claims 115-118, 120-122, 124, and 133 renders the provisional rejection of record moot for those claims. For the remaining claims, Applicant has amended independent claims 123 and 144 to each require the hapten to be selected from fluorescein, urushiol, quinone, biotin, and dinitrophenol, or a derivative thereof – which was previously presented in instant claim 127 – as well as the repeated administration of the hapten antigen presenting cell to the subject – which was previously presented in cancelled claim 124.
With that, Applicant has traversed the rejection, asserting in Pages 11-12 of the Remarks filed 17 November 2025 that copending claims 115 and 141 are different statutory categories than instant claim 123. In response, the Examiner respectfully submits that rejection over instant claim 123 relied upon copending claim 122, which is also directed to a method of treating, inhibiting, or ameliorating a cancer in a subjected involving the administration of (i) hapten- and tumor antigen-specific CAR-comprising cells, and (ii) hapten antigen presenting cells to the subject. As the instant claims and copending claims are comprised within the same statutory category, this assertion is not persuasive.
Applicant has further traversed the rejection, asserting in Page 12 of the Remarks filed 17 November 2025 that Rushworth et al relates to the restimulation of CAR-T cells in vitro, which cannot be reasonably translated to the restimulation of CAR-T cells in vivo. In response, the Examiner respectfully submits that Applicant has failed to provide substantiated evidence and/or secondary considerations as to why the ordinary artisan would not reasonably consider the results of Rushworth et al to be translatable in vivo. Accordingly, Applicant’s arguments are not persuasive, as arguments presented by Applicant cannot take the place of evidence in the record. See MPEP § 2145(I): In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.").
Therefore, the rejection over claims 123, 125-132, and 134 is maintained and amended to encompass the claims as written.
New/Maintained Grounds of Rejection
Claim Objections
Claim 136 is objected to because of the following informalities:
Regarding claim 136: The instant claim is objected for failing to include an article prior to the recitation of “peripheral blood mononuclear cell (PBMC)”.
Appropriate correction is required.
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 123, 125-127, 130-132, 135-138, and 144 are rejected under 35 U.S.C. 103 as being unpatentable over Hadrup et al (US 2019/0316069 A1, of record) in view of Lobb et al (US 2018/0311269 A1, of record) and Rushworth et al (J Immunother, 2014, of record).
Hadrup et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Lobb et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Rushworth et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 123, 127, 137, and 144: Hadrup et al disclose artificial antigen presenting cell (aAPC) scaffolds to provide cells with specific functional stimulation to obtain phenotypic and functional properties ideal to mediate tumor regression or viral clearance (Abstract).
As such, Hadrup et al disclose that the aAPC scaffolds comprise a hapten which is specifically designed to stimulate anti-hapten CAR-T cells, wherein the hapten can be conjugated with anti-cancer antibodies for the targeting of cancer antigens (Paragraphs [0066], [0068]-[0069], [0082], [0134]-[0135], [0139], [0255], [0274]-[0275], [0282]).
Hadrup et al further disclose that the hapten is fluorescein (Paragraphs [0069], [0134]).
Hadrup et al further disclose that the CAR-T cells are administered to a subject in need thereof for the treatment of cancer, while the aAPC scaffolds can be directly administered to a subject in need thereof as an immunotherapy (Paragraphs [0052], [0253], [0283], [0290], [0300], [0358]-[0359]).
Hadrup et al further disclose that the aAPC scaffolds administered to the subject are capable of efficiently expanding an antigen-specific T cell response in vivo (Paragraphs [0358]-[0359]).
Hadrup et al do not disclose that the anti-hapten CAR-T cell further comprises an additional CAR which specifically binds to a cancer antigen, nor the repeat stimulation of the CAR-T cells via administration of the aAPC scaffold, as required by instant claim 123.
Lobb et al, however, disclose T cells expressing CARs that recognize multiple targets or antigens, wherein one antigen is a self-antigen and another antigen is a non-self antigen (Paragraphs [0005], [0018]-[0020], [0057], [0069]-[0070], [0087]). Lobb et al further disclose that the self-antigens include tumor antigens, whereas the non-self antigens include haptens – specifically, green fluorescent protein (Paragraphs [0006], [0033]-[0036]).
With that, Rushworth et al disclose the repeated stimulation of CAR-T cells on culture days 7 and 14 with an antigen presenting cell expressing a universal CAR-T cell ligand that binds the conserved IgG4 exodomain of the CAR (Abstract; Pages 206-207, Propagation of…; Page 211, Discussion; Figure 1).
Therefore, it would have been prima facie obvious to have modified the treatment method of Hadrup et al such that the CAR-T cells express CARs specific for fluorescein and a tumor antigen, as detailed in Lobb et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to include a CAR that is specific for an antigen that is overexpressed in cancerous tumor cells, as it allows for the targeted treatment of the tumor, and would have had a reasonable expectation of success given that both the disclosures of Hadrup et al and Lobb et al are concerned with the expansion and utilization of CAR-T cells for the treatment of cancer (Hadrup et al: Paragraphs [0289]-[0307]; Lobb et al: Paragraphs [0029], [0073]). Thus, there would be minimal adaptation required between the two methods. See MPEP § 2143(I)(G).
Furthermore, it would have been prima facie obvious to have modified the treatment method of Hadrup et al and Lobb et al such that the aAPC scaffold is repeatedly administered to the subject in need thereof. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to provide a universal aAPC that is capable of expanding CAR-T cells independent of the CAR-T cell specificity (Rushworth et al: Page 210, CARL+ K562…), and would have had a reasonable expectation of success based on the disclosure of Hadrup et al (Paragraphs [0052], [0253], [0283], [0290], [0300], [0358]-[0359]) and ease of adaptability to the methods of Rushworth et al (Pages 205-207), especially since both concern the use of antigen presenting cell structures comprising non-self antigens. See MPEP § 2143(I)(A) and MPEP § 2143(I)(G).
Consequently, Hadrup et al as modified by Lobb et al and Rushworth et al render obvious a method of treating cancer, wherein T cells expressing CARs specific for fluorescein (claims 127, 137) and a tumor antigen are administered to a subject in need thereof, and are subsequently stimulated and/or restimulated via the repeat in vivo administration of a fluorescein aAPC scaffold. This therefore renders obvious the methods of instant claims 123 and 144.
Regarding claims 125 and 135-136: Following the discussion of claim 123, Hadrup et al further disclose another embodiment of the invention wherein autologous dendritic cells are pulsed with an antigenic peptide ex vivo to serve as antigen presenting cells for the antigen-specific T cells that are derived from the same donor (Paragraphs [0360]-[0363]; Figure 20). It is of note that dendritic cells are peripheral blood mononuclear cells (Paragraph [0360]).
Therefore, it would have been prima facie obvious to have substituted the hapten aAPC scaffold of Hadrup et al for the hapten-pulsed dendritic cells, as doing so would have been a simple substitution of one antigen presenting cell structure for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two antigen presenting cell structures are functionally comparable, as they allow for the expansion of the antigen-specific T cells (Paragraph [0363]), and would have thereby been able to substitute the antigen presenting cell structures with predictable results.
Consequently, Hadrup et al render obvious a method of treating cancer, wherein the ex vivo pulsed (claim 135) dendritic APC cells – which are inherently peripheral blood mononuclear cells (claim 136) – and T cells are derived from the same subject. This therefore renders obvious the method of instant claim 125.
Regarding claim 126: Following the discussion of claim 123, Lobb et al further disclose that the tumor antigen is CD19 (Paragraphs [0031], [0033]-[0035], [0087]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 123.
Regarding claims 130-131: Following the discussion of claim 123, Lobb et al further disclose that the T cell is a bulk CD8+ cytotoxic T cell or CD4+ T helper cell (Paragraph [0057]). This therefore reads on the method of the instant claims.
Regarding claim 132: Following the discussion of claim 123, Hadrup et al further disclose that the subject is a human (Paragraph [0289]). This therefore reads on the method of instant claim 132.
Regarding claim 135: Following the discussion of claim 123, Hadrup et al further disclose another embodiment of the invention wherein autologous dendritic cells are pulsed with an antigenic peptide ex vivo to serve as antigen presenting cells for the antigen-specific T cells that are derived from the same donor (Paragraphs [0360]-[0363]; Figure 20).
Regarding claims 138: Following the discussion of claim 126, Hadrup et al further disclose that the hapten is fluorescein (Paragraphs [0069], [0134]). This therefore reads on the method of the instant claim.
Claims 123, 125-132, 135-139, 141-142, and 144 are rejected under 35 U.S.C. 103 as being unpatentable over Hadrup et al (US 2019/0316069 A1, of record) in view of Lobb et al (US 2018/0311269 A1) and Rushworth et al (J Immunother, 2014, of record), and further in view of Jensen et al (WO 2018/148224 A1, of record), and Butler et al (Immunol Rev, 2014, of record).
The discussion of Hadrup et al as modified by Lobb et al and Rushworth et al regarding claims 123, 126, and 136 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Hadrup et al in view of Lobb et al and Rushworth et al render obvious claims 123, 125-127, 130-132, 135-138, and 144. Jensen et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 16 August 2018. Butler et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 128-129, 139, and 141-142: As aforementioned in the discussion of claims 123, 126, and 136 above, Hadrup et al as modified by Lobb et al and Rushworth et al render obvious a method of treating cancer, wherein T cells expressing CARs specific for fluorescein and a tumor antigen, as well as the fluorescein-pulsed dendritic cells are repeatedly administered to a subject in need thereof.
The combination of Hadrup et al, Lobb et al, and Rushworth et al fail to teach that the fluorescein is covalently attached to the antigen presenting cell – or dendritic cell – via a phospholipid ether, as required by instant claims 128-129 and 141.
Jensen et al, however, disclose synthetic compounds that are useful for targeting and labeling tumor cells so as to facilitate recognition by binding agents including chimeric antigen receptor (CAR) T cells (Abstract).
As such, Jensen et al disclose the joining of fluorescein to a phospholipid ether (PLE), wherein the PLE is covalently attached to the surface of a cell, particularly K562 cells (Paragraphs [0008]-[0009], [0019], [0021], [0031], [0059], [0075]-[0076], [0078], [0098]-[0099]; Figure 2). It is of note that K562 cells are well-known artificial antigen presenting cells. See Butler et al, Pages 5, 8, 15-18.
Therefore, it would have been prima facie obvious to have substituted the fluorescein antigen of Hadrup et al for the fluorescein-PLE antigen of Jensen et al, as doing so would be a simple substitution of one fluorescein antigen for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two antigens are functionally comparable, as they allow for the specific activation of the corresponding CAR-T cells when pulsed onto antigen presenting cells (Hadrup et al: Paragraphs [0332]; Jensen et al: Paragraphs [0021], [0099]), and would have thereby been able to substitute the fluorescein antigens with predictable results.
Consequently, Hadrup et al as modified by Lobb et al, Rushworth et al, Jensen et al, and Butler et al render obvious a method of treating cancer, wherein T cells expressing CARs specific for fluorescein (claims 139, 142) and a tumor antigen, as well as the fluorescein-PLE-pulsed dendritic cells are repeatedly administered to a subject in need thereof (claims 129, 141). As the fluorescein-PLE conjugate is covalently attached to the surface of the dendritic cells, this therefore renders obvious the method of instant claim 128.
Claims 123, 125-127, 130-132, 134-138, 140, and 144 are rejected under 35 U.S.C. 103 as being unpatentable over Hadrup et al (US 2019/0316069 A1, of record) in view of Lobb et al (US 2018/0311269 A1, of record) and Rushworth et al (J Immunother, 2014, of record), and further in view of Chaudhary (WO 2019/067805 A1).
The discussion of Hadrup et al as modified by Lobb et al and Rushworth et al regarding claim 123 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Hadrup et al in view of Lobb et al and Rushworth et al render obvious claims 123, 125-127, 130-132, 135-138, and 144. Chaudhary is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 134 and 140: As aforementioned in the discussion of claim 123 above, Hadrup et al as modified by Lobb et al and Rushworth et al render obvious a method of treating cancer, wherein T cells expressing CARs specific for fluorescein and a tumor antigen, as well as the fluorescein aAPC scaffold are repeatedly administered to a subject in need thereof.
The combination of Hadrup et al, Lobb et al, and Rushworth et al fail to teach that the scFv of the fluorescein CAR comprises an amino acid sequence having at least 95% sequence identity to any one of instant SEQ ID NOs: 1-6, 8, or 10, as required by instant claim 134.
Chaudhary, however, discloses polynucleotides, vectors, systems and cells comprising chimeric antigenic receptors (CARs) that promote the adoptive cell therapies of cancer (Abstract).
As such, Chaudhary discloses that the CARs comprise a fluorescein Isothiocyanate (FITC) antigen binding domain having an amino acid sequence as set forth in SEQ ID NO: 12966, which has 100% sequence identity to instant SEQ ID NO: 1 (Paragraphs [0005], [0007], [0014]-[0015], [0056], [0176]; Table 11. See sequence alignment at end of document.
Therefore, it would have been prima facie obvious to have substituted the fluorescein binding domain of Hadrup et al for the FITC binding domain of Chaudhary, as doing so would have been a simple substitution of one fluorescein binding domain for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two binding domains are functionally comparable, as they are both specific for fluorescein compounds, and would have thereby been able to substitute the binding domains with predictable results.
Consequently, Hadrup et al as modified by Lobb et al, Rushworth et al, and Chaudhary render obvious a method of treating cancer, wherein the fluorescein-specific CAR (claim 140) comprised within the T cell has an amino acid sequence as set forth in SEQ ID NO: 12966 of Chaudhary. As SEQ ID NO: 12966 of Chaudhary and instant SEQ ID NO: 1 are identical, this therefore renders obvious the method of instant claim 134.
Claims 123, 125-132, 135-139, and 141-144 are rejected under 35 U.S.C. 103 as being unpatentable over Hadrup et al (US 2019/0316069 A1, of record) in view of Lobb et al (US 2018/0311269 A1, of record), Rushworth et al (J Immunother, 2014, of record), Jensen et al (WO 2018/148224 A1, of record), and Butler et al (Immunol Rev, 2014, of record), and further in view of Chaudhary (WO 2019/067805 A1).
The discussion of Hadrup et al as modified by Lobb et al and Rushworth et al regarding claims 123, 126, and 136, and the discussion of Hadrup et al as modified by Lobb et al, Rushworth et al, Jensen et al, and Butler et al regarding claims 141-142 can each be observed above and are relied upon herein, the content of which is incorporated in its entirety. Hadrup et al in view of Lobb et al and Rushworth et al render obvious claims 123, 125-127, 130-132, 135-138, and 144. Hadrup et al in view of Lobb et al, Rushworth et al, Jensen et al, and Butler et al render obvious claims 123, 125-132, 135-139, 141-142, and 144. Chaudhary is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 143: As aforementioned in the discussion of claims 123, 126, 136, and 141-142 above, Hadrup et al as modified by Lobb et al, Rushworth et al, Jensen et al, and Butler et al render obvious a method of treating cancer, wherein T cells expressing CARs specific for fluorescein and a tumor antigen, as well as the fluorescein-PLE-pulsed dendritic cells are repeatedly administered to a subject in need thereof.
The combination of Hadrup et al, Lobb et al, Rushworth et al, Jensen et al, and Butler et al fail to teach that the scFv of the fluorescein CAR comprises an amino acid sequence having at least 95% sequence identity to any one of instant SEQ ID NOs: 1-4, as required by instant claim 143.
Chaudhary, however, discloses polynucleotides, vectors, systems and cells comprising chimeric antigenic receptors (CARs) that promote the adoptive cell therapies of cancer (Abstract).
As such, Chaudhary discloses that the CARs comprise a fluorescein Isothiocyanate (FITC) binding domain having an amino acid sequence as set forth in SEQ ID NO: 12966, which has 100% sequence identity to instant SEQ ID NO: 1 (Paragraphs [0005], [0007], [0014]-[0015], [0056], [0176]; Table 11. See sequence alignment at end of document.
Therefore, it would have been prima facie obvious to have substituted the fluorescein binding domain of Hadrup et al for the FITC binding domain of Chaudhary, as doing so would have been a simple substitution of one fluorescein binding domain for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two binding domains are functionally comparable, as they are both specific for fluorescein compounds, and would have thereby been able to substitute the binding domains with predictable results.
Consequently, Hadrup et al as modified by Lobb et al, Rushworth et al, Jensen et al, Butler et al, and Chaudhary render obvious a method of treating cancer, wherein the fluorescein-specific CAR (claim 140) comprised within the T cell has an amino acid sequence as set forth in SEQ ID NO: 12966 of Chaudhary. As SEQ ID NO: 12966 of Chaudhary and instant SEQ ID NO: 1 are identical, this therefore renders obvious the method of the instant claim.
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.
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Claims 123, 125-132, and 134-144 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 115, 120-122, 128, 135, and 140 of copending Application No. 17/265,484 in view of Rushworth et al (J Immunother, 2014, of record), Lobb et al (US 2018/0311269 A1, of record), Hadrup et al (US 2019/0316069 A1, of record), and Chaudhary (WO 2019/067805 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending 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 copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, 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.
Copending claim 122 is directed to a method of treating, inhibiting, or ameliorating a cancer in a subject, comprising:
(i) administering to the subject an effector cell comprising a first chimeric antigen receptor (CAR) and a second CAR, wherein the first CAR and the second CAR are encoded by one or more nucleic acids, the one or more nucleic acids comprising:
a first sequence encoding the first CAR, wherein the first CAR comprises a first ligand binding domain specific for a tumor antigen, a first polypeptide spacer, a first transmembrane domain and a first intracellular signaling domain; and
a second sequence encoding the second CAR, wherein the second CAR comprises a second ligand binding domain specific for a hapten, a second polypeptide spacer, a second transmembrane domain and a second intracellular signaling domain; and
(ii) administering to the H-APC to the subject a hapten antigen presenting cell (H-APC), wherein the H-APC comprises a hapten covalently attached to a phospholipid integrated into the plasma membrane of the H-APC, and wherein the hapten is selected from fluorescein, urushiol, quinone, biotin, and dinitrophenol, or a derivative thereof;
wherein the second CAR of the effector cell is capable of directly binding the hapten of the H-APC.
It is of note that the combination of the effector cell and H-APC as detailed in copending claim 122 are equivalent to the system as claimed in copending claim 115.
With that, copending claim 120 further limits the system of copending claim 115 such that the effector cell is a T cell.
The copending application does not disclose the repeated stimulation of the CAR-T cells with the H-APC, as required by instant claim 123.
Rushworth et al, however, disclose the repeated stimulation of CAR-T cells on culture days 7 and 14 with an antigen presenting cell expressing a universal CAR-T cell ligand that binds the conserved IgG4 exodomain of the CAR (Abstract; Pages 206-207, Propagation of…; Page 211, Discussion; Figure 1).
Therefore, it would have been prima facie obvious to have modified the treatment method of copending claim 122 such that the H-APC is repeatedly administered to the subject in need thereof. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to provide a universal aAPC that is capable of expanding CAR-T cells independent of the CAR-T cell specificity (Rushworth et al: Page 210, CARL+ K562…), and would have had a reasonable expectation of success based on the methods of the copending claims and ease of adaptability to the methods of Rushworth et al (Pages 205-207), especially since both concern the use of antigen presenting cell structures comprising non-self antigens. See MPEP § 2143(I)(A) and MPEP § 2143(I)(G).
Consequently, this renders obvious the method of instant claims 123, 127-128, 137, and 144.
Copending claim 135 further limits the system of copending claim 115, wherein the effector cell and the H-APC are derived from a single subject. This therefore renders obvious the method of instant claim 125 when considering the method of copending claim 122.
Copending claim 140 further limits the system of copending claim 115, wherein the phospholipid is a phospholipid ether (PLE). This therefore renders obvious the method of instant claims 129 and 141 when considering the method of copending claim 122.
Copending claim 121 further limits the system of copending claim 115, wherein the effector cell is (a) a CD8+ T cytotoxic lymphocyte cell selected from the group consisting of a naive CD8+ T cell, a central memory CD8+ T cell, an effector memory CD8+ T cell and a bulk CD8+ T cell;(b) a CD4+ T helper lymphocyte cell selected from the group consisting of a naive CD4+ T cell, a central memory CD4+ T cell, an effector memory CD4+ T cell, and a bulk CD4+ T cell; or (c) a precursor T cell or a hematopoietic stem cell. This therefore renders obvious the method of instant claims 130-131 when considering the method of copending claim 122.
Copending claim 128 further limits the system of copending claim 115, wherein the hapten is fluorescein or a derivative thereof. This therefore renders obvious the method of instant claims 138-140 and 142 when considering the method of copending claim 122.
With that, instant claims 126, 132, 134-136, and 143 are known from the prior art and can be further incorporated into the method rendered obvious by copending claims 115, 120, and 122:
Lobb et al further teach the limitations recited in instant claim 126.
Hadrup et al further teach the limitations recited in instant claims 132 and 135-136.
Chaudhary further teaches the limitations recited in instant claims 134 and 143.
This is a provisional nonstatutory double patenting rejection.
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).
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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.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
Sequence Alignment
Query Match 100.0%; Matches 251; Mismatches 0; Indels 0; Gaps 0
Qy 1 SVLTQPSSVSAAPGQKVTISCSGSTSNIGNNYVSWYQQHPGKAPKLMIYDVSKRPSGVPD 60
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Db 22 SVLTQPSSVSAAPGQKVTISCSGSTSNIGNNYVSWYQQHPGKAPKLMIYDVSKRPSGVPD 81
Qy 61 RFSGSKSGNSASLDISGLQSEDEADYYCAAWDDSLSEFLFGTGTKLTVLGGGGGSGGGGS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 82 RFSGSKSGNSASLDISGLQSEDEADYYCAAWDDSLSEFLFGTGTKLTVLGGGGGSGGGGS 141
Qy 121 GGGGSQVQLVESGGNLVQPGGSLRLSCAASGFTFGSFSMSWVRQAPGGGLEWVAGLSARS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 142 GGGGSQVQLVESGGNLVQPGGSLRLSCAASGFTFGSFSMSWVRQAPGGGLEWVAGLSARS 201
Qy 181 SLTHYADSVKGRFTISRDNAKNSVYLQMNSLRVEDTAVYYCARRSYDSSGYWGHFYSYMD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 202 SLTHYADSVKGRFTISRDNAKNSVYLQMNSLRVEDTAVYYCARRSYDSSGYWGHFYSYMD 261
Qy 241 VWGQGTLVTVS 251 (INSTANT SEQ ID NO: 1)
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Db 262 VWGQGTLVTVS 272 (CHAUDHARY SEQ ID NO: 12966)