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 .
Detailed Action
This action is in response to the papers filed August 14, 2025.
Claim Amendments
Applicant’s amendment to the claims filed on 08/14/2025 is acknowledged.
Claims 1-12, and 22 are cancelled.
Claims 13-21 are pending.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claim 21 is under examination.
Noncompliance with 37 CFR 1.121(c):
Applicant’s amendment to the claims filed on 08/14/2025 does not comply with one or more of the requirements of 37 CFR 1.121(c). In this case, regarding the markings for claim 21, line 8 indicates that the word “and” is both deleted (double brackets) and added (underlined) to the claim when, in fact, said word was not previously presented in claim 21; lines 11-12 indicate that the phrase “wherein the method does not” was previously presented (no markings) when, in fact, said phrase is newly added to claim 21; and line 12 indicates that the phrase “exposing the cells to an anti-CD3 antibody” is deleted (strike-through) when, in fact, said phrase was not previously presented in claim 21. Nonetheless the present amendment has been entered in an effort to advance prosecution of the application. Applicant is respectfully reminded to comply with the requirements of 37 CFR 1.121(c) when making amendments to the claims in order to avoid potential delays in prosecution.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See the Requirement for Restriction/Election mailed 10/09/2024.
Applicant elected without traverse Invention II, drawn to a population of cells or T cell product, in the reply filed 01/09/2025.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/09/2025.
Priority
The instant application 18/424,395 was filed on 01/26/2024. This application is a continuation (CON) of U.S. Application No. 17/141,142 filed 01/04/2021, which is a CON of U.S. Application No. 15/561,921 filed 09/26/2017, which is a national stage of international application PCT/US2016/024560 filed 03/28/2016, claiming priority based on U.S. Provisional Application No. 62/138,942 filed 03/26/2015.
Claim Objections
Claim 21 is objected to because of the following informalities:
The preamble of claim 21 recites “prepared by by a method.” The repetitive “by by” should be corrected. Appropriate action is required.
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 21 is rejected under 35 U.S.C. 103 as being unpatentable over Peggs et al. (2011) “Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation” Clinical infectious diseases, 52(1), 49-57; in view of Wang et al. (2012) "Enhanced Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV Specific Central Memory T Cells by CMV Vaccine" Blood 120(21):3014; and Klebanoff et al. (2004) “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells” Proceedings of the National Academy of Sciences, 101(7), 1969-1974.
This rejection is newly applied, necessitated by amendment.
Peggs discloses a population of T cells produced by a process comprising:
providing peripheral blood mononuclear cells (PBMCs) from a cytomegalovirus (CMV) seropositive human donor;
exposing the PBMCs to CMV-antigen pp65 to provide a population of CMV antigen-exposed PBMC; and
enriching the population of CMV antigen-exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population,
wherein the process does not include CD3 stimulation.
See Abstract; see Selection of IFN-γ–Secreting Cells on page 50.
Peggs does not disclose that the γ-enriched, CMV-specific T cells are transduced with a nucleic acid encoding a chimeric antigen receptor (CAR), as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Wang discloses a population of CMV-specific CAR-T cells produced by a process comprising: providing PBMCs from a CMV seropositive donor; exposing the PBMCs derived to CMV pp65 antigen ("CMV specific T cells derived from central memory T cells were selectively expanded by 2 rounds of stimulation with cGMP grade pp65 protein"); transducing at least a portion of the enriched population of cells with a vector expressing anti-CD19 CAR ("then transduced with cGMP grade SIN lentivirus expressing CD19R:CD28:z/EG FRt"), thereby preparing T cells specific for CMV and expressing a CAR.
Wang further teaches that “engineering CMV specific T cells with CD19CAR to provide them with a second specificity for a tumor antigen may enable the transferred T cells (bispecific T cells) to persist or numerically expand in vivo by stimulation of the endogenous TCR by virus antigen” and “bi-specific T cell can be used in treatment for B cell malignancies in allo-settings without causing GVHD due to the pre-defined non-alloreactive TCR specificity.” In conclusion, Wang reports that “[t]he findings demonstrated that CD19CAR modified CMV specific T cells are capable of responding to viral antigen reactivation through their endogenous TCR, which could be used to magnify the antitumor activity of CAR transduced T cells in vivo.”
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the CMV-specific T cell product of Peggs by further transducing the cells with a nucleic acid encoding a CAR polypeptide, as taught by Wang, with a reasonable expectation of success because CAR polypeptides improve antitumor activity of adoptively transferred T cells, and CAR-T cells comprising a CMV-specific TCR may persist or numerically expand in vivo by stimulation of the endogenous TCR by virus antigen.
Process step of IL-15 supplemented cell culture:
Claim 21 further recites a process step of culturing the population of transduced cells in culture medium comprising IL-15.
Peggs and Wang do not describe a process step of culturing the T cells in a medium containing IL-15, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Klebanoff teaches that cell culture media containing IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred (Abstract; Discussion on pg. 1974).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of making a T cell product, as found in Peggs and Wang, to further include a step of culturing the T cell population in medium containing IL-15, as found in Klebanoff, with a reasonable expectation of success because IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred.
Negative limitation excluding CD3 stimulation:
Claim 21 recites the negative limitation wherein the process of making does not include CD3 stimulation.
Peggs successfully generated CMV-specific T cells without including CD3 stimulation in the process (pg. 50, paragraph bridging columns). Therefore, Peggs is found to meet the instantly recited negative limitation.
Wang successfully generated bi-specific “CMVxCD19CAR” T cells but discloses that the CMV-specific T cells are stimulated with “OKT3” (i.e., an anti-CD3 antibody) prior to transduction with the nucleic acid encoding the CD19CAR.
Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
In this case, the claim recites that the bispecific T cells are made by a process which does not include CD3 stimulation. Although Wang includes CD3 stimulation in the process, Peggs demonstrates that CMV-specific T cells may be produced without CD3 stimulation. Moreover, the negative limitation excluding CD3 stimulation is a product-by-process limitation that is not found to necessarily confer or imply a structure that patentably distinguishes the instantly claimed bi-specific T cells from those found in Wang.
For these reasons, the product-by-process limitation where “the method does not include CD3 stimulation,” as recited by claim 21, is not found to patentably distinguish the instantly claimed invention over the cited references.
The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983). See MPEP 2113.
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.
Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,116,834 B2; in view of Peggs et al. (2011) “Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation” Clinical infectious diseases, 52(1), 49-57; and Klebanoff et al. (2004) “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells” Proceedings of the National Academy of Sciences, 101(7), 1969-1974. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the patent claims and secondary references.
This rejection is newly applied, necessitated by amendment.
Patent claim 1 recites a method using a population of human T cells expressing a CMV-specific TCR and a recombinant CAR polypeptide.
Patent claim 8 recites that the bispecific T cells are made by a process comprising:
isolating PBMCs from a CMV-seropositive human donor;
contacting the PBMCs with at least one CMV antigen;
allowing said contacted cells to produce a population of cells enriched for stimulated cells specific for CMV; and
transducing at least a portion of the enriched population of cells with a vector expressing a recombinant CAR protein, thereby forming a population of human T cells expressing a CMV-specific TCR and a recombinant CAR protein.
The patent claims do not recite that the T cells are enriched for cells expressing IFN-γ, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Peggs discloses a population of CMV-specific T cells produced by a process comprising:
providing PBMCs from a CMV seropositive human donor;
exposing the PBMCs to CMV-antigen pp65 to provide a population of CMV antigen-exposed PBMC; and
enriching the population of CMV antigen-exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
See Abstract; see Selection of IFN-γ–Secreting Cells on page 50.
Peggs further teaches that application of CMV-specific T cells generated by direct selection using IFN- γ capture is “both feasible and effective in a clinical environment” and these “simple in vitro methodologies should allow more widespread application of virus-specific T cell immunotherapies” (Abstract).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the T cell product of the patent claims by enriching for CMV-specific cells expressing IFN-γ, as taught by Peggs, with a reasonable expectation of success because IFN-γ capture is a convenient and technically simple procedure for the isolation and enrichment of CMV-specific T cells for use in adoptive transfer.
Neither the patent clams nor Peggs disclose that the process includes CD3 stimulation. Accordingly, the cited references are found to meet the negative limitation “the method does not include CD3 stimulation,” as instantly claimed in claim 21.
Claim 21 further recites a process step of culturing the population of transduced cells in culture medium comprising IL-15.
Neither the patent claims nor Peggs disclose a process step of culturing the T cells in a medium containing IL-15, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Klebanoff teaches that cell culture media containing IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred (Abstract; Discussion on pg. 1974).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of making a T cell product, as found in the patent claims and Peggs, to further include a step of culturing the T cell population in medium containing IL-15, as found in Klebanoff, with a reasonable expectation of success because IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred.
Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,690,908 B2; in view of Peggs et al. (2011) “Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation” Clinical infectious diseases, 52(1), 49-57; and Klebanoff et al. (2004) “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells” Proceedings of the National Academy of Sciences, 101(7), 1969-1974. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the patent claims and secondary references.
This rejection is newly applied, necessitated by amendment.
Patent claim 2 recites a method of making a population of human T cells expressing a CMV-specific TCR and a recombinant CAR polypeptide, wherein the bispecific T cells are produced by a process comprising:
isolating PBMCs from a CMV-seropositive human donor;
contacting the PBMCs with at least one CMV antigen;
allowing said contacted cells to produce a population of cells enriched for stimulated cells specific for CMV; and
transducing at least a portion of the enriched population of cells with a vector expressing a recombinant CAR protein, thereby forming a population of human T cells expressing a CMV-specific TCR and a recombinant CAR protein.
The patent claims do not recite that the T cells are enriched for cells expressing IFN-γ, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Peggs discloses a population of CMV-specific T cells produced by a process comprising:
providing PBMCs from a CMV seropositive human donor;
exposing the PBMCs to CMV-antigen pp65 to provide a population of CMV antigen-exposed PBMC; and
enriching the population of CMV antigen-exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
See Abstract; see Selection of IFN-γ–Secreting Cells on page 50.
Peggs further teaches that application of CMV-specific T cells generated by direct selection using IFN- γ capture is “both feasible and effective in a clinical environment” and these “simple in vitro methodologies should allow more widespread application of virus-specific T cell immunotherapies” (Abstract).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the T cell product of the patent claims by enriching for CMV-specific cells expressing IFN-γ, as taught by Peggs, with a reasonable expectation of success because IFN-γ capture is a convenient and technically simple procedure for the isolation and enrichment of CMV-specific T cells for use in adoptive transfer.
Neither the patent clams nor Peggs disclose that the process includes CD3 stimulation. Accordingly, the cited references are found to meet the negative limitation “the method does not include CD3 stimulation,” as instantly claimed in claim 21.
Claim 21 further recites a process step of culturing the population of transduced cells in culture medium comprising IL-15.
Neither the patent claims nor Peggs disclose a process step of culturing the T cells in a medium containing IL-15, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Klebanoff teaches that cell culture media containing IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred (Abstract; Discussion on pg. 1974).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of making a T cell product, as found in the patent claims and Peggs, to further include a step of culturing the T cell population in medium containing IL-15, as found in Klebanoff, with a reasonable expectation of success because IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred.
Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,161,714 B2; in view of Peggs et al. (2011) “Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation” Clinical infectious diseases, 52(1), 49-57; and Klebanoff et al. (2004) “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells” Proceedings of the National Academy of Sciences, 101(7), 1969-1974. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the patent claims and secondary references.
This rejection is newly applied, necessitated by amendment.
Patent claim 1 recites a cell comprising a TCR specific for a CMV antigen and a recombinant CAR protein.
The patent claims do not expressly recite that the cell is a T cell or that the cell is transduced with a nucleic acid encoding the CAR protein. "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). In this case, one of ordinary skill in the art would have reasonably inferred that the cell is a T cell because the cell expresses a T cell receptor (TCR) and a CAR protein comprising an “intracellular T-cell signaling domain” (claim 4). In addition, the term “recombinant” indicates that expression of the CAR polypeptide is produced by introduction of exogenous nucleic acids encoding the CAR polypeptide.
The patent claims do not recite that the CMV-specific cell is produced by a process comprising:
providing PBMC from a cytomegalovirus (CMV) seropositive human donor;
exposing the PBMC to at least one CMV antigen to provide a population of CMV antigen exposed PBMC; and
enriching the population of CMV antigen exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
Prior to the effective filing date of the instantly claimed invention, Peggs discloses a population of CMV-specific T cells produced by a process comprising:
providing PBMCs from a CMV seropositive human donor;
exposing the PBMCs to CMV-antigen pp65 to provide a population of CMV antigen-exposed PBMC; and
enriching the population of CMV antigen-exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
See Abstract; see Selection of IFN-γ–Secreting Cells on page 50.
Peggs further teaches that application of CMV-specific T cells generated by direct selection using IFN- γ capture is “both feasible and effective in a clinical environment” and these “simple in vitro methodologies should allow more widespread application of virus-specific T cell immunotherapies” (Abstract).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the T cell product of the patent claims by obtaining the T cell product from a process comprising exposing PBMCs obtained from a CMV-seropositive donor to a CMV antigen and enriching for cells expressing IFN-γ, as taught by Peggs, with a reasonable expectation of success because the process of producing CMV-specific T cells enriched by IFN-γ capture, as found in Peggs, is a convenient and technically simple procedure for the isolation and enrichment of CMV-specific T cells for use in adoptive transfer.
Neither the patent clams nor Peggs disclose that the process includes CD3 stimulation. Accordingly, the cited references are found to meet the negative limitation “the method does not include CD3 stimulation,” as instantly claimed in claim 21.
Claim 21 further recites a process step of culturing the population of transduced cells in culture medium comprising IL-15.
Neither the patent claims nor Peggs disclose a process step of culturing the T cells in a medium containing IL-15, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Klebanoff teaches that cell culture media containing IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred (Abstract; Discussion on pg. 1974).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of making a T cell product, as found in the patent claims and Peggs, to further include a step of culturing the T cell population in medium containing IL-15, as found in Klebanoff, with a reasonable expectation of success because IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred.
Claim 21 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 18/354,849 (reference to claim listing filed 07/03/2025); in view of Peggs et al. (2011) “Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation” Clinical infectious diseases, 52(1), 49-57; and Klebanoff et al. (2004) “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells” Proceedings of the National Academy of Sciences, 101(7), 1969-1974. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the copending claims and secondary references. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection is newly applied, necessitated by amendment.
Copending claim 51 recites a method of using a population of T cells expressing a CAR polypeptide and a CMV-specific TCR.
Copending claim 58 recites that the bispecific T cells are produced by a process comprising:
providing PBMC from a CMV-seropositive human donor;
exposing the PBMC to at least one CMV antigen;
treating the exposed cells to produce an enriched population of cells expressing a CMV-specific TCR; and
transducing at least a portion of the enriched cell population with a vector expressing a CAR protein.
The copending claims do not recite that the T cells are enriched for cells expressing IFN-γ, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Peggs discloses a population of CMV-specific T cells produced by a process comprising:
providing PBMCs from a CMV seropositive human donor;
exposing the PBMCs to CMV-antigen pp65 to provide a population of CMV antigen-exposed PBMC; and
enriching the population of CMV antigen-exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
See Abstract; see Selection of IFN-γ–Secreting Cells on page 50.
Peggs further teaches that application of CMV-specific T cells generated by direct selection using IFN-γ capture is “both feasible and effective in a clinical environment” and these “simple in vitro methodologies should allow more widespread application of virus-specific T cell immunotherapies” (Abstract).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the T cell product of the copending claims by enriching for CMV-specific cells expressing IFN-γ, as taught by Peggs, with a reasonable expectation of success because IFN-γ capture is a convenient and technically simple procedure for the isolation and enrichment of CMV-specific T cells for use in adoptive transfer.
Neither the patent clams nor Peggs disclose that the process includes CD3 stimulation. Accordingly, the cited references are found to meet the negative limitation “the method does not include CD3 stimulation,” as instantly claimed in claim 21.
Claim 21 further recites a process step of culturing the population of transduced cells in culture medium comprising IL-15.
Neither the patent claims nor Peggs disclose a process step of culturing the T cells in a medium containing IL-15, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Klebanoff teaches that cell culture media containing IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred (Abstract; Discussion on pg. 1974).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of making a T cell product, as found in the patent claims and Peggs, to further include a step of culturing the T cell population in medium containing IL-15, as found in Klebanoff, with a reasonable expectation of success because IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred.
Claim 21 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 16/758,516 (reference to claim listing filed 07/10/2025); in view of Peggs et al. (2011) “Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation” Clinical infectious diseases, 52(1), 49-57; and Klebanoff et al. (2004) “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells” Proceedings of the National Academy of Sciences, 101(7), 1969-1974. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the copending claims and secondary references. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection is newly applied, necessitated by amendment.
Copending claims 56 recites a population of T cells expressing a CMV-specific TCR and comprising a nucleic acid molecule encoding a CAR protein.
The copending claims do not recite that the bispecific T cell is produced by a process comprising:
providing PBMC from a cytomegalovirus (CMV) seropositive human donor;
exposing the PBMC to at least one CMV antigen to provide a population of CMV antigen exposed PBMC; and
enriching the population of CMV antigen exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
Prior to the effective filing date of the instantly claimed invention, Peggs discloses a population of CMV-specific T cells produced by a process comprising:
providing PBMCs from a CMV seropositive human donor;
exposing the PBMCs to CMV-antigen pp65 to provide a population of CMV antigen-exposed PBMC; and
enriching the population of CMV antigen-exposed PBMC for cells expressing interferon gamma (IFN-γ) to produce an enriched cell population.
See Abstract; see Selection of IFN-γ–Secreting Cells on page 50.
Peggs further teaches that application of CMV-specific T cells generated by direct selection using IFN-γ capture is “both feasible and effective in a clinical environment” and these “simple in vitro methodologies should allow more widespread application of virus-specific T cell immunotherapies” (Abstract).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the T cell product of the copending claims by obtaining the T cell product from a process comprising exposing PBMCs obtained from a CMV-seropositive donor to a CMV antigen and enriching for cells expressing IFN-γ, as taught by Peggs, with a reasonable expectation of success because the process of producing CMV-specific T cells enriched by IFN-γ capture, as found in Peggs, is a convenient and technically simple procedure for the isolation and enrichment of CMV-specific T cells for use in adoptive transfer.
Neither the patent clams nor Peggs disclose that the process includes CD3 stimulation. Accordingly, the cited references are found to meet the negative limitation “the method does not include CD3 stimulation,” as instantly claimed in claim 21.
Claim 21 further recites a process step of culturing the population of transduced cells in culture medium comprising IL-15.
Neither the patent claims nor Peggs disclose a process step of culturing the T cells in a medium containing IL-15, as instantly claimed.
Prior to the effective filing date of the instantly claimed invention, Klebanoff teaches that cell culture media containing IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred (Abstract; Discussion on pg. 1974).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the process of making a T cell product, as found in the patent claims and Peggs, to further include a step of culturing the T cell population in medium containing IL-15, as found in Klebanoff, with a reasonable expectation of success because IL-15 expands tumor-reactive T cells in vitro and enhances their in vivo antitumor activity when adoptively transferred.
Incomplete response:
Applicant’s reply states that the nonstatutory double patenting (NSDP) rejections will be addressed upon notification that the claims are otherwise allowable (pg. 6). As instructed by MPEP 804, a complete response to a NSDP rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims or the filing of a terminal disclaimer in accordance with 37 CFR 1.321. Such a response is required even when the nonstatutory double patenting rejection is provisional. Accordingly, applicant’s reply filed 08/14/2025 is not in compliance with 37 CFR 1.111(b), which requires a complete reply to every ground of objection and rejection set forth in the prior Office action. Applicant is respectfully reminded to provide a complete reply to every ground of objection and rejection, as required by 37 CFR 1.111(b), in order to avoid delays prosecution.
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 JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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, James D Schultz can be reached on (571)272-0763. 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.
/JAMES JOSEPH GRABER/Examiner, Art Unit 1631