DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment, filed 07/31/2026, has been entered.
Claims 1-8, 10-11, 15, 17-19, 22, 31, 38, 44, 50 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I and species with further administration of lymphodepleting chemotherapy in the reply filed on 07/31/2026 is acknowledged.
Claims 31, 38, 44, 50 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites languages of percent likelihood of specified outcomes. The claim does not identify whether recited percent likelihood refers to a predicted probability for an individual patient or an outcome rate in a population of treated patients. The specification provides no definition of “likelihood” that resolves this ambiguity. These interpretations render the claim indefinite. For example, a method used to treat one patient who achieves complete response might satisfy a limitation directed to that patient’s outcome, but that observation would not establish a 55% outcome rate in a treated population or a 55% predicted probability for the patient. Accordingly, a person of ordinary skill in the art cannot determine which methods fall within the scope of claim 3. Applicant is required to clarify what the percentage measures and the population, if any, to which it applies. See MPEP § 2173.02.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6, 15, and 22 are rejected under 35 U.S.C. § 102(a)(1) as anticipated by Borchmann et al. (HemaSphere 6(Suppl):1070–1071 (2022) including Poster P1184; the report was presented at EHA2022 on June 9–17, 2022)
Regarding claims 1 and 2, Borchmann describes collecting autologous cells by leukapheresis, transducing CD4 and CD8 T cells with a lentiviral vector encoding a CD19/CD20 CAR, expanding the cells, and infusing the resulting fresh product into the patient. Borchmann reports a mean interval of 14 days from leukapheresis to infusion, within the claimed 28 days. See Introduction; Results—MB-CART2019.1 manufacturing; Fig. 2. For claim 2’s patient population, Borchmann expressly identifies patients in dose level 2 as having relapsed or refractory diffuse large B-cell lymphoma (DLBCL). See poster P1184 Study population and patient characteristics.
Furthermore, preamble language in the present claims of the instant application directed to "preventing and/or reducing the likelihood of prolonged thrombocytopenia” is an expression of purpose and intended result, and as such are non-limiting, since language does not result in manipulative difference in the step of the claims. It does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. In re Hirao 190 USPQ 15, 16-17, (CCPA 1976) held that the preamble was non-limiting because it merely recited the purpose of the process, which was fully set forth in the body of the claim.
Regarding claim 3, Borchmann taught 5 patients had complete response and have completed the 2-year follow-up visit without evidence of relapse. See poster P1184 Conclusion. Under the broadest reasonable interpretation, these patients meet the limitations of claim 3.
Regarding claim 4, Borchmann’s mean leukapheresis-to-infusion interval of 14 days meets the expressly listed “not longer than 14 days” alternative. See Results—MB-CART2019.1 manufacturing and Fig. 2.
Regarding claim 5, Borchmann administers fludarabine and cyclophosphamide as lymphodepleting chemotherapy on days −5 to −3 for dose level 1, and fludarabine on days −5 to −3 with cyclophosphamide on day −5 for dose level 2. These schedules meet the claimed timing relative to infusion. See Methods—Study design.
Regarding claim 6, Borchmann states that the leukapheresis material was not cryopreserved before shipment and that the final drug product was not cryopreserved when shipped for infusion. Its Fig. 2 depicts cell selection, activation, transduction, expansion, formulation, and fresh infusion in the manufacturing sequence. See Results—MB-CART2019.1 manufacturing and Fig. 2.
Regarding claim 15, Borchmann identifies the cells used to make MB-CART2019.1 as autologous CD4 and CD8 T cells. See Introduction.
Regarding claim 17, Borchmann discloses dose level 1 (DL1), in which patients received 1.0 × 10⁶ CAR T cells/kg body weight in a single infusion. The administered CAR T cells are cultured lymphocytes, and 1.0 × 10⁶ cells/kg is the inclusive upper endpoint of the claimed range of 10,000 to 1,000,000 cultured lymphocytes/kg. Accordingly, Borchmann teaches the dose recited in claim 17.
Regarding claim 22, Borchmann states that the lentiviral vector encodes a CAR construct directed to CD19 and CD20. See Introduction and Fig. 1.
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 7 is rejected under 35 U.S.C. 103 as being unpatentable over Borchmann et al. (HemaSphere 6(Suppl):1070–1071 (2022) including Poster P1184) in view of Ghassemi et al. (Cancer Immunol Res 2018 6(9):1100-1109).
The teachings of Borchmann have been discussed supra (see above 102).
Borchmann teaches the method of claim 2, including transduction, culture, and fresh infusion of autologous CAR T cells within the claimed apheresis-to-infusion period, but does not specify the duration of culture after transduction. Ghassemi teaches harvesting CAR T cells on day 3, 48 hours after lentiviral transduction, and reports improved functional properties with shortened ex vivo culture (page 1104, Early-harvested CAR T cells exhibit enhanced effector function and proliferation). It would have been obvious to shorten Borchmann’s post-transduction culture to approximately 48 hours to obtain those reported benefits while further expediting treatment.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary
Claims 8, 10, and 11 are rejected under 35 U.S.C. §103 as unpatentable over Borchmann et al. in view of OriGen Biomedical (PermaLife Cell Culture Bags, brochure ML13.01.R02 2019), Tumaini et al. (Cryotherapy 2013; 15:1406-1415) and Dodo et al. (PLOS ONE 2014 Vol 9 e86275).
The teachings of Borchmann have been discussed supra (see above 102).
Regarding claim 8, Borchmann does not identify an incubation vessel having an inner surface area of at least 1,500 cm². OriGen’s PermaLife brochure identifies the PL750-2G cell-culture bag and gives the active compartment dimensions as 29.2 cm × 26.4 cm. Counting its two interior faces yields 1,541.76 cm² (Techincal Information). Dodo expressly counts the top and bottom faces when specifying a PermaLife bag’s surface area and teaches that both faces can be used for vector adsorption (page 3 Scaled-up transduction using the RBV-LTS method). It would have been obvious to select OriGen’s larger bag to provide additional closed-system culture capacity and surface for transduction.
Regarding claim 10, Dodo teaches coating PermaLife bags with recombinant human fibronectin fragment RetroNectin (RN) to increase the efficiency of retrovirual transduction (Discussion). Additionally, Tumanini taught using RN in a 10 μg/mL coating solution (Methods Generation of clinical grade anti-CD19-CAR-transductetd T cell). It would have been obvious to use that established coating on the selected PermaLife bag to facilitate viral transduction.
Regarding claim 11, Dodo teaches contacting the inner surface of a RetroNectin-coated PermaLife bag with a second solution comprising retroviral vector, using 180 mL of vector solution (Methods Generation of clinical grade anti-CD19-CAR-transductetd T cell). A person of ordinary skill adapting that process to the larger PL750-2G bag would have had reason to use about 200 mL as a modest adjustment of the known vector-loading volume. The record identifies 180 mL as Dodo’s disclosed value; the conclusion that about 200 mL would have been selected is the proposed obviousness inference.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 18 and 19 are rejected under 35 U.S.C. §103 as unpatentable over Borchmann et al. (PermaLife Cell Culture Bags, brochure ML13.01.R02 2019) in view of Posey et al. (US 2020/0306304 A1) and Tumaini et al. (Cryotherapy 2013; 15:1406-1415).
Regarding claim 18, Borchmann teaches administering CAR T cells at defined dose levels, including DL1 at 1 × 10⁶ CAR T cells/kg, but does not expressly teach the recited narrower range of 20,000–400,000 total cultured lymphocytes/kg. Posey teaches selecting administered total T-cell doses within 10⁵–10⁶ cells/kg and expressly identifies 2 × 10⁵ cells/kg (paragraph 0470). Posey’s range overlaps the recited range, and its stated 200,000 cells/kg value falls within it. In selecting a dose for Borchmann’s engineered T-cell treatment, a person of ordinary skill would have had reason to evaluate Posey’s expressly disclosed lower total-cell dose.
Regarding claim 19, Tumaini reports a mean 68% transduction efficiency in an anti-CD19 CAR T-cell manufacturing process, exceeding recited requirement that at least 15% of the cultured lymphocytes be transduced. A person of ordinary skill preparing the product for administration at the dose taught by Posey would have had reason to use Tumaini’s known transduction approach to obtain a therapeutically useful engineered-cell fraction, with a reasonable expectation of exceeding 15%.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/SHARON X WEN/Primary Examiner, Art Unit 1641
