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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 03/16/2026 has been entered.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 03/16/2026 has been received and considered.
Status of the Claims
Claims 5-6, 8-22, and 24-26 are pending.
Claims 5-6, 8-22, and 24-26 have been examined on their merits.
Withdrawn Actions
Due to the Information Disclosure Statement (IDS) submitted on 03/16/2026 in reconsideration of the claims, the previous Notice of Allowance send on 03/11/2026 is withdrawn in order to address Karyampudi et al. (WO2018209115, published 11/15/2018, filed 05/10/2018) and Tran et al (WO2016053338A1, on IDS 03/16/2026) as cited in the IDS.
Claim Objections
Claim 19 is objected to for the following informalities: claim 19 recites “of_claim” – the underlining should be removed.
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.
Claims 5-6, 8, 10, 15, 19-22, and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Karyampudi et al. (WO2018209115, published 11/15/2018, filed 05/10/2018, on IDS 03/16/2026).
In regards to claim 5, Karyampudi teaches a method (process) for expanding peripheral blood lymphocytes (PBLs) from a whole blood samples (claim 60; paragraph [00151]).
In regards to step (a), Karyampudi teaches obtaining PBMCs from whole blood from a patient having a liquid tumor (claim 60, paragraphs [00126-00127, 00182]).
Karyampudi is silent as to the specific amount of blood obtained from a liquid tumor.
However, a person of ordinary skill in the art could have arrived at an amount of 50 mL by routine optimization and the disclosure does not point to a criticality in this amount (see MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
In the instant case since Karyampudi teaches that in other embodiments immune cells (including lymphocytes specifically) can be expanded from 10-50 mL of bone marrow aspirates obtained from a patient (paragraph [00198]), which overlaps with the claimed amount, it could have been done with predictable results and a reasonable expectation of success.
In regards to step (b), Karyampudi teaches that the cells are cultured (admixed) with beads selective for CD3 and CD28 (claim 60). Karyampudi teaches that the cells can be cultured at a ratio of 3 beads : 1 cell (paragraph [00191]).
In regards to step (c), Karyampudi teaches that the beads and about 2.5 x 105 to about 5 x 105 cells are cultured on a gas-permeable container in a medium comprising IL-2 between 3 to 6 days (claim 60) . A timing of 3 to 6 days overlaps with the claimed range of about 4 days.
In regards to the density of the cells, Karyampudi teaches that the term “about” can be “within an order of magnitude” (paragraph [00149]). Thus, a range of “about 2.5 x 105 to about 5 x 105 cells” reads on a broad range of 2.5 x 104 to 5 x 106 cells.
In regards to the density of cell per cm, in embodiments Karyampudi teaches that a G-Rex 100 which has a 100 cm2 gas permeable culture surface may be used (paragraph [00224]). On a 100 cm2 gas permeable culture surface, a population 5 x 106 cells results in 50,000 cells per cm2 which overlaps with the claimed density.
In regards to step (d), Karyampudi teaches that the cells can be further cultured in a second medium that comprises IL-2 between 3 to 6 days (claim 60). A timing of 3 to 6 days overlaps with the claimed range of about 5 days.
In regards to step (e), Karyampudi teaches that the cells are harvested (claim 60).
In regards to claim 6, in regards to the total number of harvested cells, Karyampudi teaches the expansion process can yield between 1.6 x 108 (160 million) to 20 x 109 (20 billion) PBLs (paragraph [00180], which overlaps with the claimed range of 8 to 15 billion.
In regards to claims 8 and 9, Karyampudi teaches that the beads selective for CD3 and CD28 are beads conjugated to anti-CD3 antibodies and anti-CD28 antibodies (paragraph [0014], e.g., anti-body coated Dynabeads). It is noted that it is well-known in the art that Dynabeads are magnetic beads that function by forming complexes with targeted cells. Additionally, Karyampudi teaches that these beads are separated with a magnet and cells counted (paragraphs [00152, 00169]. A person of ordinary skill in the art would have recognized the complexed cells would also be removed in this process.
In regards to claims 10 and 15, Karyampudi teaches that B cells can be removed from the PBLs (claim 61; paragraph [00178]). In regards to the order of the specific step of removing B cells (whether after step (d) or before step (b), Applicant should note that 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 (IV)(C)). In the instant case a person of ordinary skill in the art would have been motivated to remove B cells after expansion in order to have a purer population of lymphocytes (e.g., T cells). Furthermore, because Karyampudi teaches that B cells can be removed, it could have been done with predictable results and a reasonable expectation of success.
In regards to claims 19 and 20, Karyampudi teaches that the concentration of IL-2 is 3000 IU/mL in each of the steps (paragraph [0013]).
In regards to claim 21, in embodiments Karyampudi teaches that TILs (lymphocytes) can be cultured in flasks containing IL-2 in conditions of 37°C and 5% CO2 (paragraph [00235]). A person of ordinary skill in the art would have been motivated to culture PBLs under these conditions because Karyamputi indicates that there are suitable for culturing lymphocytes. Furthermore, because Karyamputi cultures lymphocytes under conditions of 37°C and 5% CO2 in the presence of IL-2 for the expansion of lymphocytes, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 22, the timing of the expansion appears to be minimally about 4 days (claims 38; paragraph [0008) (stimulating and culturing steps only take about 2 days each). Additionally, in other similar embodiments Karyamputi teaches that expansion can be performed over a period of between 3 to 11 days, which also overlaps with the claimed range of about 9 days.
In regards to claims 24 and 25, Karyampudi teaches that the patient can be pretreated with an ITK inhibitor and specifically ibrutinib (claims 60-66).
In regards to claims 26, Karyampudi teaches that the patient is suffering from chronic lymphocytic leukemia.
Therefore, Karyampudi renders the invention unpatentable as claimed.
Claims 11-14 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Karyampudi et al. (WO2018209115, published 11/15/2018, filed 05/10/2018, on IDS 03/16/2026) as applied to claims 5 and 10 above, and further in view of Tran et al (WO2016053338A1, on IDS 03/16/2026).
In regards to claim 11-14 and 16-18, Karyampudi teaches that CD19+ B cells are selected for and can be removed from the PBLs using binding to (magnetic) beads (claim 61; paragraph [00178]), and removed with a magnet a magnet (paragraphs [00152, 00169]). While Karyampudi is silent as to the mechanism of their selection, Karyampudi teaches the use of selective Dynabeads throughout the specification (paragraph [00182, etc.]), and therefore, a person of ordinary skill in the art would have recognized that Karyampudi is referring to CD19-selective beads. Furthermore, because Tran teaches that CD19 (conjugated) microbeads (from Miltenyi which are well-known magnetic beads) can be used to select B cells (paragraph [0086]), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Karyampudi and Tran render the invention unpatentable as claimed.
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 5-6, 8-22, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of co-pending Application No. 18/182,676 in view of Karyampudi et al. (WO2018209115, published 11/15/2018, filed 05/10/2018, on IDS 03/16/2026) and Tran et al (WO2016053338A1, on IDS 03/16/2026).
Although the conflicting claims of co-pending Application No. 18/182,676 are not identical to the currently prosecuted claims, they are not patentably distinct because said claims of both inventions are drawn to methods for preparing (expanding, culturing, and harvesting over a range that overlaps with 5 to 7 days) peripheral blood lymphocytes from blood comprising obtaining samples of blood from a patient with a liquid tumor comprising stimulating PBLs in a culture medium with IL-2 (at 3000 IU/mL) and anti-CD3/28 antibodies, and treating a patient with an ITK inhibitor such as ibrutinib. Co-pending Application No. 18/182,676 also teaches that about 2.5x105 to about 5x105 cells are added to a gas-permeable container.
While co-pending Application No. 18/182,676 does not explicitly teach that less than or equal to 50mL of blood were drawn from a patient, as discussed above, a person of ordinary skill in the art could have arrived at an amount of 50 mL by routine optimization and the disclosure does not point to a criticality in this amount (see MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
In the instant case since Karyampudi, who teaches similar methods for expanding PBLs, teaches that in other embodiments immune cells (including lymphocytes specifically) can be expanded from 10-50 mL of bone marrow aspirates obtained from a patient (paragraph [00198]), which overlaps with the claimed amount, it could have been done with predictable results and a reasonable expectation of success.
While co-pending Application No. 18/182,676 does not explicitly teach adding beads at bead to cell ratio of 3:1, it would have been predictably obvious to culture cells with beads at this ratio because as above, Karyampudi indicates that this is sufficient for stimulating PBLs (paragraph [00191]).
Additionally, while co-pending Application No. 18/182,676 does not explicitly teach steps of removing remnant B cells from the expanded population or by doing so with beads selective for CD19 and conjugated to anti-CD19 antibodies, as discussed above, a person of ordinary skill in the art would have been motivated to remove B cells in order to provide a purer population of cells (e.g., T cells), Furthermore, because as above, Karyampudi teaches that CD19+ B cells are selected for and can be removed from the PBLs using binding to (magnetic) beads (claim 61; paragraph [00178]) and removed with a magnet (paragraphs [00152, 00169]), and because Tran teaches that CD19 (conjugated) microbeads (from Miltenyi which are well-known magnetic beads) can be used to select B cells (paragraph [0086]), it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 5-6, 8-22, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-57 of co-pending Application No. 18/674,418 in view of Karyampudi et al. (WO2018209115, published 11/15/2018, filed 05/10/2018, on IDS 03/16/2026) and Tran et al (WO2016053338A1, on IDS 03/16/2026).
Although the conflicting claims of co-pending Application No. 18/674,418 are not identical to the currently prosecuted claims, they are not patentably distinct because said claims of both inventions are drawn to methods for preparing PBLs from the whole blood of a patient with a liquid tumor (including leukemias) comprising obtaining a sample of PBMCs from a patient, wherein the patient has been treated with an ITK inhibitor such as ibrutinib, admixing those cells with anti-CD3 and anti-CD28 antibodies complexed to magnetic beads in a 3:1 ratio, culturing cells in first and second media comprising 3000 IU/mL IL-2 under conditions of 37°C and 5% CO2 over a span of overlapping days.
While co-pending Application No. 18/674,418 is silent as to the amount of blood drawn from a patient, as discussed above, a person of ordinary skill in the art could have arrived at an amount of 50 mL by routine optimization and the disclosure does not point to a criticality in this amount (see MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
In the instant case since Karyampudi, who teaches similar methods for expanding PBLs, teaches that in other embodiments immune cells (including lymphocytes specifically) can be expanded from 10-50 mL of bone marrow aspirates obtained from a patient (paragraph [00198]), which overlaps with the claimed amount, it could have been done with predictable results and a reasonable expectation of success.
Additionally, while co-pending Application No. 18/674,418 is silent as to the seeding densities, as discussed above, a person of ordinary skill in the art could have arrived at the claims seeding densities and the disclosure does not point to a criticality in this amount.
As discussed above, seeding densities for expansion of PBLs was known in the art. As discussed above, Karyampudi teaches that the beads and about 2.5 x 105 to about 5 x 105 cells are cultured on a gas-permeable container in a medium comprising IL-2 between 3 to 6 days (claim 60). Karyampudi teaches that the term “about” can be “within an order of magnitude” (paragraph [00149]). Thus, a range of “about 2.5 x 105 to about 5 x 105 cells” reads on a broad range of 2.5 x 104 to 5 x 106 cells.
In regards to the density of cell per cm, in embodiments Karyampudi teaches that a G-Rex 100 which has a 100 cm2 gas permeable culture surface may be used (paragraph [00224]). On a 100 cm2 gas permeable culture surface, a population 5 x 106 cells results in 50,000 cells per cm2 which overlaps with the claimed density.
Therefore, a person of ordinary skill in the art could have arrived at the claimed seeding density by routine optimization with predictable results and a reasonable expectation of success.
Furthermore, a person of ordinary skill in the art would have been predictable obvious to use a culture vessel with a gas-permeable surface because Karyampudi teaches that these vessels can expand billions of cells (paragraphs [0306-0308]) and demonstrates that 1.6 x 108 (160 million) to 20 x 109 (20 billion) expanded PBLs can be obtained (paragraph [00180]).
Additionally, while co-pending Application No. 18/674,418 does not explicitly teach steps of removing remnant B cells from the expanded population or by doing so with beads selective for CD19 and conjugated to anti-CD19 antibodies, as discussed above, a person of ordinary skill in the art would have been motivated to remove B cells in order to provide a purer population of cells (e.g., T cells), Furthermore, because as above, Karyampudi teaches that CD19+ B cells are selected for and can be removed from the PBLs using binding to (magnetic) beads (claim 61; paragraph [00178]) and removed with a magnet (paragraphs [00152, 00169]), and because Tran teaches that CD19 (conjugated) microbeads (from Miltenyi which are well-known magnetic beads) can be used to select B cells (paragraph [0086]), it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 03/16/2026 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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