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 April 22, 2025.
Claim Amendments
Applicant’s amendment to the claims filed 04/22/2025 is acknowledged.
Claims 1-12 are pending.
Claims 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claims 1-7 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the present application. See Office action mailed 01/30/2025.
Applicant elected with traverse the invention of Group 1, claims 1-7, drawn to a method of preparing a population of CD7-CD3+ T cells, during a telephone conversation on 01/14/2025. See interview summary mailed 01/30/2025. The election was affirmed by applicant is the reply filed 04/22/2025.
Claims 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction/election requirement during a telephone conversation on 01/14/2025.
Priority
The instant application 17/783,040 was filed on 06/07/2022. This application is a national stage of international application PCT/US2020/063259 filed 12/04/2020, claiming priority based on U.S. Provisional Application 62/945,267 filed 12/09/2019.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 01/30/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Declaration under 37 CFR 1.130(a):
The declaration of Mireya Paulina Velasquez under 37 CFR 1.130(a), filed on 04/22/2025, is acknowledged. The declaration is found sufficient to disqualify as prior art the disclosure of Freiwan et al. (13 Nov 2019) “Engineering Naturally Occurring CD7 Negative Cells for the Immunotherapy of CD7 Positive Leukemia” Blood, Volume 134, Supplement 1, page 868. Accordingly, the previous rejections under 35 U.S.C. 102 and 35 U.S.C. 103 relying upon this disclosure have been withdrawn.
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.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/213979 A1 to Bari et al.
This rejection is newly applied. Applicant’s remarks filed 04/22/2025 have been carefully considered, but are found moot in view of the new grounds of rejection.
Regarding claims 1-3 and 6, Bari teaches methods of producing genetically modified T cells comprising an exogenous nucleic acid encoding an anti-CD7 chimeric antigen receptor (CAR). See, e.g., paragraphs 4, 52; claim 9.
In the working examples, CD7- cells are isolated from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting (MASCs) and transduced with an anti-CD7 CAR polypeptide. See paragraphs 5-8, 65-68; figures 1-3. In particular, figure 1 shows sorting of PBMCs based on CD3 and CD7 expression:
PNG
media_image1.png
476
462
media_image1.png
Greyscale
Figure 1 shows obtainment of a CD3+CD7- cell population (top left) and a CD3-CD7- cell population (bottom left). CD3 is a marker of the T cell lineage, and therefore the CD3+CD7- cell population represents the T cell population. Moreover, in paragraph 45, Bari teaches that T cells are isolated from peripheral blood lymphocytes, and a subpopulation of T cells, such as CD3+ T cells, are further isolated by positive or negative selection techniques. As discussed above, Bari teaches negative selection of CD7- T cells for making anti-CD7 CAR-T cells. For these reasons, Bari is found to teach or fairly suggest the selection of CD3+CD7- T cells.
Bari further teaches that the T cells are cultured under stimulating conditions prior to or after genetic modification of the T cells to express the CAR polypeptide. See, e.g., paragraph 49. "[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). See MPEP 2144.01. In this case, the T cells must be contained in a vessel because otherwise the T cells would be lost to the environment.
In summary, Bari teaches a method for preparing a population of CD3+CD7- T cells comprising:
obtaining a population of primary immune cells,
performing a selection comprising enriching cells that express CD3 and depleting cells that express CD7 thereby generating a population of CD3+CD7- T cells,
incubating the population of CD3+CD7- T cells in a culture vessel under stimulating conditions thereby generating stimulated T cells, and
genetically modifying the stimulated T cells by introducing nucleic acids encoding a chimeric antigen receptor (CAR).
The difference between Bari’s method and the method of claims 1-3 and 6 is the claimed order of performing process steps. In particular, although Bari teaches that a population of primary immune cells is depleted of CD7+ cells and enriched for CD3+ cells, Bari does not teach that the population of primary immune cells are first depleted of CD7+ cells and then enriched for CD3+ cells, as claimed in claims 1-3 and 6. However, the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). See MPEP 2144.04. In this case, one of ordinary skill in the art would have recognized that, in a process of selecting for CD3+CD7- T cells, as taught by Bari, the population of primary immune cells are either (1) first enriched for CD3+ cells and then depleted of CD7+ cells or (2) first depleted of CD7+ cells and then enriched for CD3+ cells (as instantly claimed). Moreover, regardless of the order of performing process steps, one of ordinary skill in the art would have reasonably expected the same result, i.e., isolation of the CD3+CD7- T cell population from the starting population of primary immune cells. For these reasons, absent new or unexpected results, the order of performing process steps is not found to patentably distinguish the instantly claimed invention from that found in the Bari disclosure. For these reasons, the claimed order of performing process steps, i.e., CD7- selection followed by CD3+ selection, would have been prima facie obvious over the prior art.
The claims further recite that, after the selection and stimulation steps, the T cells exhibit a phenotype of being CD7-negative, CD3-positive, CD4-postive, CCR7-negative and CD45RA-negative (claims 1, 3 and 7). Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. In this case, the recitation describes a functional characteristic or intended result which naturally flows from performing the process steps positively recited in the claimed method. The recitation does not clearly limit the claimed method to a particular structure or manipulative action that patentably distinguishes the claimed method from the teachings of the prior art. As set forth above, the positively-recited selection and stimulation steps would have been prima facie obvious over the Bari disclosure, and therefore the recited CD7-CD3+ CD4+CCR7-CD45RA- phenotype would also naturally flow from the teachings of the prior art. Indeed, as discussed above, Bari teaches CD7-CD3+ selection of T cells. Therefore, Bari’s T cells necessarily possess the CD7-CD3+ phenotype. In addition, applicant’s specification demonstrates that CD7-CD3+ selection of T cells produces a T cell population having a CD4+CCR7-CD45RA- phenotype (par. 12 and 102, and Fig. 4). Accordingly, CD7-CD3+ selection of T cells, as found in the Bari disclosure, would also naturally produce T cells having a CD4+CCR7-CD45RA- phenotype. For these reasons, the recitation of a CD7-CD3+CD4+CCR7-CD45RA- T cell phenotype (claims 1, 3 and 7) is not found to patentably distinguish the claimed method from the teachings of the prior art.
For these reasons, claims 1-3 and 6 would have been prima facie obvious over the prior art.
Regarding claims 4-5, Bari teaches that the selection comprises immunoaffinity-based selection using an antibody immobilized on or attached to a magnetic particle or label. See, e.g., paragraphs 45, 52, 65-68.
Claim 7 further describes the first selection step as comprising (i) contacting the population of primary immune cells with a first immunoaffinity reagent that specifically binds to CD7 on the surface of the primary immune cells and (ii) recovering cells for the population that are not bound to the first immunoaffinity reagent to enrich for CD7- cells, and the second selection step as comprising (i) contacting the population of CD7- cells with a second immunoaffinity reagent that specifically binds to CD3 on the surface of CD7-negative cells and (ii) recovering T cells of the population that are bound to the second immunoaffinity reagent to enrich for CD7-CD3+ T cells. For positive selection of CD3+ cells, Bari teaches that the cells are isolated by incubation with anti-CD3/anti-CD28-conjugated beads (par. 45), and therefore enrichment for CD3+ cells entails recovery of cells bound to the beads from the population. For negative selection of CD7- cells, Bari teaches that the cells are isolated by incubation with an anti-CD7 antibody, and unlabeled cells (i.e., CD7- cells) are separated from cells labeled with the anti-CD7 antibody (par. 52, 65-68). As discussed above, figure 1 shows recovery of CD3+CD7- T cells from PBMCs. For these reasons, and those provided above, claim 7 would have been prima facie obvious over the Bari disclosure.
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 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,390,658 B2; in view of WO 2017/213979 A1 to Bari et al.
This rejection is newly applied. Applicant’s remarks filed 04/22/2025 have been carefully considered, but are found moot in view of the new grounds of rejection.
Patent claim 5 recites a method of producing an anti-CD7 CAR-T cell comprising,
obtaining a population of CD7- T cells, and
transducing the CD7- T cells with a nucleic acid construct encoding an anti-CD7 CAR.
The patent claims do not recite that the method of producing an anti-CD7 CAR-T cell comprises:
performing a first selection comprising depleting, from a population of primary immune cells, cells that express CD7 thereby generating a population of CD7- cells, and
performing a second selection comprising enriching, from the population of CD7- cells, T cell that express CD3 thereby generating a population of CD3+CD7- T cells.
WO 2017/213979 A1 is the publication of the international application corresponding to U.S. Patent No. 11,390,658 B2. Therefore, the same disclosure is found in WO 2017/213979 A1 and U.S. Patent No. 11,390,658 B2. WO 2017/213979 A1 qualifies as prior art.
WO 2017/213979 A1 teaches methods of producing genetically modified T cells comprising an exogenous nucleic acid encoding an anti-CD7 chimeric antigen receptor (CAR). See, e.g., paragraphs 4, 52; claim 9.
In the working examples, CD7- cells are isolated from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting (MASCs) and transduced with an anti-CD7 CAR polypeptide. See paragraphs 5-8, 65-68; figures 1-3. In particular, figure 1 shows sorting of PBMCs based on CD3 and CD7 expression:
PNG
media_image1.png
476
462
media_image1.png
Greyscale
Figure 1 shows obtainment of a CD3+CD7- cell population (top left) and a CD3-CD7- cell population (bottom left). CD3 is a marker of the T cell lineage, and therefore the CD3+CD7- cell population represents the T cell population. Moreover, in paragraph 45, WO 2017/213979 A1 teaches that T cells are isolated from peripheral blood lymphocytes, and a subpopulation of T cells, such as CD3+ T cells, are further isolated by positive or negative selection techniques. As discussed above, WO 2017/213979 A1 teaches negative selection of CD7- T cells for making anti-CD7 CAR-T cells. For these reasons, WO 2017/213979 A1 is found to teach or fairly suggest the selection of CD3+CD7- T cells.
In summary, WO 2017/213979 A1 teaches a method for preparing a population of CD3+CD7- T cells comprising:
obtaining a population of primary immune cells,
performing a selection comprising enriching cells that express CD3 and depleting cells that express CD7, thereby generating a population of CD3+CD7- T cells, and
genetically modifying the T cells by introducing nucleic acids encoding a chimeric antigen receptor (CAR).
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 method of the patent claims by including the selection steps for obtaining CD3+CD7- T cells found in WO 2017/213979 A1 and outlined above (i.e., performing a selection comprising enriching cells that express CD3 and depleting cells that express CD7, thereby generating a population of CD3+CD7- T cells), with a reasonable expectation of success because patent claim 5 recites obtaining CD7- T cells for making anti-CD7 CAR-T cells, and CD3 is a marker of the T cell lineage used for isolation of T cells from a population of primary immune cells, e.g., from a sample of peripheral blood.
Although WO 2017/213979 A1 teaches that a population of primary immune cells is depleted of CD7+ cells and enriched for CD3+ cells, WO 2017/213979 A1 does not teach that the population of primary immune cells are first depleted of CD7+ cells and then enriched for CD3+ cells, as instantly claimed in claims 1, 3 and 7. However, the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). See MPEP 2144.04. In this case, one of ordinary skill in the art would have recognized that, in a process of selecting for CD3+CD7- T cells, as taught by WO 2017/213979 A1, the population of primary immune cells are either (1) first enriched for CD3+ cells and then depleted of CD7+ cells or (2) first depleted of CD7+ cells and then enriched for CD3+ cells (as instantly claimed). Moreover, regardless of the order of performing process steps, one of ordinary skill in the art would have reasonably expected the same result, i.e., isolation of the CD3+CD7- T cells from the starting population of primary immune cells. For these reasons, absent new or unexpected results, the claimed order of performing process steps, i.e., CD7- selection followed by CD3+ selection, would have been prima facie obvious over the cited references.
Claims 1-3, 6-7 further recite that the cells are incubated in a culture vessel under stimulating conditions prior to genetic modification. WO 2017/213979 A1 further teaches that the T cells are cultured under stimulating conditions prior to or after genetic modification of the T cells to express the CAR polypeptide. See, e.g., paragraph 49. "[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). See MPEP 2144.01. In this case, the T cells must be contained in a vessel because otherwise the T cells would be lost to the environment.
The instant claims further recite that, after the selection and stimulation steps, the T cells exhibit a phenotype of being CD7-negative, CD3-positive, CD4-postive, CCR7-negative and CD45RA-negative (claims 1, 3 and 7). Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. In this case, the recitation describes a functional characteristic or intended result which naturally flows from performing the process steps positively recited in the instant claims. The recitation does not clearly limit the instantly claimed method to a particular structure or manipulative action that patentably distinguishes the instantly claimed method from the teachings of the cited references. As set forth above, the positively-recited selection and stimulation steps would have been prima facie obvious over the cited references, and therefore the recited CD7-CD3+CD4+CCR7-CD45RA- phenotype would also naturally flow from the teachings of the cited references. Indeed, as discussed above, WO 2017/213979 A1 teaches CD7-CD3+ selection of T cells. Therefore, the T cells of WO 2017/213979 A1 necessarily possess the CD7-CD3+ phenotype. In addition, the instant specification demonstrates that CD7-CD3+ selection of T cells produces a T cell population having a CD4+CCR7-CD45RA- phenotype (par. 12 and 102, and Fig. 4). Accordingly, CD7-CD3+ selection of T cells, as found in the WO 2017/213979 A1 disclosure, would also naturally produce T cells having a CD4+CCR7-CD45RA- phenotype. For these reasons, the recitation of a CD7-CD3+CD4+CCR7-CD45RA- T cell phenotype (claims 1, 3 and 7) is not found to patentably distinguish the instantly claimed method from the teachings of the cited references.
For these reasons, instant claims 1-3 and 6 would have been prima facie obvious over the patent claims and cited secondary references.
Regarding claims 4-5, WO 2017/213979 A1 teaches that the selection comprising immunoaffinity-based selection using an antibody immobilized on or attached to a magnetic particle or label. See, e.g., paragraphs 45, 52, 65-68.
Claim 7 further defines the first selection step as comprising (i) contacting the population of primary immune cells with a first immunoaffinity reagent that specifically binds to CD7 on the surface of the primary immune cells and (ii) recovering cells for the population that are not bound to the first immunoaffinity reagent to enrich for CD7- cells, and the second selection step as comprising (i) contacting the population of CD7- cells with a second immunoaffinity reagent that specifically binds to CD3 on the surface of CD7-negative cells and (ii) recovering T cells of the population that are bound to the second immunoaffinity reagent to enrich for CD7-CD3+ T cells. For positive selection of CD3+ cells, WO 2017/213979 A1 teaches that the cells are isolated by incubation with anti-CD3/anti-CD28-conjugated beads (par. 45), and therefore enrichment for CD3+ cells entails recovery of cells bound to the beads from the population. For negative selection of CD7- cells, WO 2017/213979 A1 teaches that the cells are isolated by incubation with an anti-CD7 antibody, and unlabeled cells (i.e., CD7- cells) are separated from cells labeled with the anti-CD7 antibody (par. 52, 65-68). As discussed above, figure 1 of WO 2017/213979 A1 shows recovery of CD3+CD7- T cells from PBMCs. For these reasons, and those provided above, claim 7 would have been prima facie obvious over the cited references.
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