The examiner for the application has changed, please address all future communications to Francesca Edgington-Giordano, AU 1643.
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 final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 20 February 2026 has been entered.
Claim Status
Claims 4-5, 7-12, 14, 16-20, 22-28, 30-32, 34-52, 54-59, 61-64, 68-69, 71, 74-77, 79, 81-86, 88, 90, 92, 94, 98-100, 102-116, and 125 are cancelled. Claims 1-3, 6, 13, 15, 21, 29, 33, 53, 60, 65-67, 70, 72-73, 78, 80, 87, 89, 91, 93, 95-97, 101, 117-124, and 126-130 as filed on 20 February 2026 are pending and under examination.
Rejections and Objections Withdrawn
Rejection of claim 29 under 35 U.S.C. 112(b) is withdrawn with applicant amendment of claims.
Rejection of claims 1-3, 6, 13, 15, 21, 29, 33, 65-67, 70, 72, 73, 78-80, 87, 89, 91, 93, 95-97, 101, 102, and 117-126 under 35 U.S.C. 103 over “WO101” and Riddell are withdrawn with applicant amendment of claims.
Rejection of claims 53 and 60 under 35 U.S.C. 103 over “WO101”, Riddell, and Christodoulou are withdrawn with applicant amendment of claims.
Applicant arguments filed 02/20/2026 have been considered, but as they are to rejections that have not been maintained no response to arguments are made.
New Rejections
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 6, 13, 21, 29, 33, 65, 70, 72-73, 78, 80, 87, 89, 93, 95-97, 118-119, and 126-129 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beauchesna (WO 2018106732 A1) (PTO-892), as evidenced by Nascimbeni et. al. Blood. 104(2):478-486 (2004) (PTO-892) and Rahemtulla et. al. Am J Clin Pathol. 126:805-814 (2006) (PTO-892).
Regarding claims 1 and 6, Beauchesne teaches a method of genetically engineering cells including into chimeric antigen receptor producing cells (abstract). Beauchesne teaches the cells are CD3+ ([0015]). Beauchesne teaches the administration of 5 x 106 cells to 100 x 106 cells (0423]). Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18). Beauchesne specifically teaches the input composition that can be at least 80% pure can be memory T cells ([0081]), thus teaching memory T cells that are positive for CD3+, CCR7+, and CD45RA at 80% or higher purity. Beauchesne teaches a target antigen of CD19 ([0053]) and the treatment of non-Hodgkin lymphoma ([0401]-[0402]). Beauchesne teaches embodiments where the cells are not expanded ex vivo or the cells are expanded in vivo ([0038], [0064], [0077], [0087], [00378], [0380]). Beauchesne teaches repeatedly that ex vivo expansion does not need to be done and that in vivo expansion can be done for their genetically modified CAR T cells.
Regarding claim 2, the claim requires all the elements of instant claim 1 which Beauchesne teaches as shown in the rejection of that claim and further requires the cells have at or at least about 65% CD4+ CAR T cells and at least about 65% CD8+ CAR T cells. The specification states about includes ±20% (specification page 17 in final paragraph), for instant claim 2 the about 65% would then include 52% to 78%. The claims then require at least 52% of the cells be CD4+ and at least 52% of the cells be CD8+. The 1:1 ratio of CD4+ to CD8+ cells (claim 21 of Beauchesne) would recite cell compositions and teach at least 50% identity of CD4+ and CD8+ cells. The cells of Beauchesne are memory T cells that express CD3+, CCR7+, and CD45RA+([0133]) and are autologous from patients with multiple B cell lymphoma’s including NHL or allogenic ([0401]-[0402] and [0413]) including allogenic from health donors ([0547]). The remaining at least 2% of cells would be dual positive for CD4 and CD8 and would inherently be present among autologous or allogenic memory T cells, as evidenced by Nascimbeni (Figure 1) and Rahemtulla (abstract and Image 1).
Regarding claim 3, Beauchesne teaches a ratio of about 1:2 or about 2:1 for CD4+ and CD8+ T cells ([0017] and claim 21). Instant claim 3 is to about 1:2.5 or 2.5 to 1. The specification states about includes ±20% (specification page 17 in final paragraph), instant claim 3 would then include 1:2 to 1:3 and 2:1 to 3:1 as ratios when reciting 1:2.5 and 2.5:1.
Regarding claim 13, Beauchesne teaches the use of T cell subpopulations including central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]). Beauchesne further teaches the enrichment of input cells to 90% or higher ([0350] and claim 18).
Regarding claim 21, Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18).
Regarding claim 29, Beauchesne teaches a ratio of about 1:1 to about 1:30 or 3:1 for CD4+ and CD8+ T cells ([0017] and claim 21), teaching the at least 50% mixture as required by the claim.
Regarding claim 33, Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18).
Regarding claim 65, Beauchesne teaches the treatment of PMBCL ([0402]).
Regarding claims 70 and 72, Beauchesne teaches the administration of lymphodepleting therapy before administration of the engineered CAR T cells by outpatient delivery ([0494]).
Regarding claim 73, Beauchesne teaches the administration of fludarabine at 30 mg/m2 for 3 to 5 days and cyclophosphamide at 300 mg/m2 for 3 days ([0496]-0498]).
Regarding claim 78, Beauchesne teaches the T cells are autologous ([0413]-0414]).
Regarding claim 80, Beauchesne teaches the T cells are autologous ([0413]-0414]). Beauchesne teaches the treatment of NHL ([0402]) and teaches all of the active method steps of instant claim 1 and claim 80 and would thus teach the requirement of generating a cell product for administering to the patient population of instant claim 80 as required by lines pasted below.
PNG
media_image1.png
84
648
media_image1.png
Greyscale
Regarding claims 87 and 119, Beauchesne teaches the CAR t comprises an extracellular antigen-binding domain, a transmembrane domain, an intracellular signaling domain of CD3 zeta, and a costimulatory domain (0033]-[0034]) and further teaches the antigen to be bound is CD19 ([0053]). Beauchesne teaches the signaling domain of 4-1BB in the CAR ([0246]).
Regarding claim 89, Beauchesne teaches the extracellular antigen-binding domain is an scFv ([0208]).
Regarding claim 93, Beauchesne teaches a CD28 transmembrane domain ([0033]).
Regarding claim 95-96, Beauchesne teaches a spacer domain between the extracellular antigen-binding domain and the transmembrane domain and further teaches the spacer is an immunoglobulin hinge ([0234]).
Regarding claim 97, Beauchesne teaches a spacer domain of SEQ ID NO: 27 which is ESKYGPPCPPCP which matches instant SEQ ID NO: 1 (page 174).
Regarding claim 118, Beauchesne teaches the components of the composition of claim 118 and claim 1 and the active method steps of claim 1. the instructions do not change the physical characteristics of the pharmaceutical composition of the claims making the addition of instructions anticipated (see MPEP 2112.01).
Regarding claims 126-127, Beauchesne teaches the total incubation with a stimulating agents I between 1 and 96 hours ([0377]) with no ex vivo expansion ([0378]) and further teaches the entire process of engineering the cells including selection, enrichment, incubation with transduction, is carried out in no more than 2 days which would be less than 120 hours as required by the claim ([0379]).
Regarding claims 128-129, Beauchesne teaches a target antigen of CD19 ([0053]) and the treatment of non-Hodgkin lymphoma ([0401]-[0402]). Beauchesne teaches embodiments where the cells are not expanded ex vivo or the cells are expanded in vivo ([0038], [0064], [0077], [0087], [00378], [0380]). Beauchesne teaches the CAR T comprises an extracellular antigen-binding domain, a transmembrane domain, an intracellular signaling domain of CD3 zeta, and a costimulatory domain (0033]-[0034]) and further teaches the antigen to be bound is CD19 ([0053]). Beauchesne teaches the signaling domain of 4-1BB in the CAR ([0246]). Beauchesne teaches a ratio of about 1:2 or about 2:1 for CD4+ and CD8+ T cells ([0017] and claim 21). Beauchesne teaches the administration of 5 x 106 cells to 100 x 106 cells (0423]). Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18). Beauchesne specifically teaches the input composition that can be at least 80% pure can be memory T cells ([0081]), thus teaching memory T cells that are positive for CD3+, CCR7+, and CD45RA at 80% or higher purity. Beauchesne teaches the total incubation with a stimulating agents I between 1 and 96 hours ([0377]) with no ex vivo expansion ([0378]) and further teaches the entire process of engineering the cells including selection, enrichment, incubation with transduction, is carried out in no more than 2 days which would be less than 120 hours as required by the claim ([0379]).
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.
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 1, 15, 66-67, 87, 89, 91, 95-96, 101, 117, 120-124, and 128-130 are rejected under 35 U.S.C. 103 as being unpatentable over Beauchesna (WO 2018106732 A1) (PTO-892) and Albertson (WO2018/223101A1) (IDS).
Regarding claim 1, Beauchesne teaches a method of genetically engineering cells including into chimeric antigen receptor producing cells (abstract). Beauchesne teaches the cells are CD3+ ([0015]). Beauchesne teaches the administration of 5 x 106 cells to 100 x 106 cells (0423]). Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18). Beauchesne specifically teaches the input composition that can be at least 80% pure can be memory T cells ([0081]), thus teaching memory T cells that are positive for CD3+, CCR7+, and CD45RA at 80% or higher purity. Beauchesne teaches a target antigen of CD19 ([0053]) and the treatment of non-Hodgkin lymphoma ([0401]-[0402]). Beauchesne teaches embodiments where the cells are not expanded ex vivo or the cells are expanded in vivo ([0038], [0064], [0077], [0087], [00378], [0380]). Beauchesne teaches repeatedly that ex vivo expansion does not need to be done and that in vivo expansion can be done for their genetically modified CAR T cells.
Regarding claim 87, Beauchesne teaches the CAR t comprises an extracellular antigen-binding domain, a transmembrane domain, an intracellular signaling domain of CD3 zeta, and a costimulatory domain (0033]-[0034]) and further teaches the antigen to be bound is CD19 ([0053]). Beauchesne teaches the signaling domain of 4-1BB in the CAR ([0246]).
Regarding claim 89, Beauchesne teaches the extracellular antigen-binding domain is an scFv ([0208]).
Regarding claim 95-96, Beauchesne teaches a spacer domain between the extracellular antigen-binding domain and the transmembrane domain and further teaches the spacer is an immunoglobulin hinge ([0234]).
Regarding claims 91 and 101, instant SEQ ID NO: 4 is a spacer domain and matches SEQ ID NO: 30 of Beauchesne, instant SEQ ID NO: 8 is a transmembrane domain and matches SEQ ID NO: 34 of Beauchesne, instant SEQ ID NO: 12 is a 4-1BB co-stimulatory domain and matches SEQ ID NO: 36 of Beauchesne, instant SEQ ID NO: 13 is a CD3 zeta signaling domain and matches SEQ ID NO: 39 of Beauchesne (table on pages 173-176).
Regarding claims 128-129, Beauchesne teaches a target antigen of CD19 ([0053]) and the treatment of non-Hodgkin lymphoma ([0401]-[0402]). Beauchesne teaches embodiments where the cells are not expanded ex vivo or the cells are expanded in vivo ([0038], [0064], [0077], [0087], [00378], [0380]). Beauchesne teaches the CAR T comprises an extracellular antigen-binding domain, a transmembrane domain, an intracellular signaling domain of CD3 zeta, and a costimulatory domain (0033]-[0034]) and further teaches the antigen to be bound is CD19 ([0053]). Beauchesne teaches the signaling domain of 4-1BB in the CAR ([0246]). Beauchesne teaches a ratio of about 1:2 or about 2:1 for CD4+ and CD8+ T cells ([0017] and claim 21). Beauchesne teaches the administration of 5 x 106 cells to 100 x 106 cells (0423]). Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18). Beauchesne specifically teaches the input composition that can be at least 80% pure can be memory T cells ([0081]), thus teaching memory T cells that are positive for CD3+, CCR7+, and CD45RA at 80% or higher purity. Beauchesne teaches the total incubation with a stimulating agents I between 1 and 96 hours ([0377]) with no ex vivo expansion ([0378]) and further teaches the entire process of engineering the cells including selection, enrichment, incubation with transduction, is carried out in no more than 2 days which would be less than 120 hours as required by the claim ([0379]).
Beauchesne does not teach the measurement of apoptosis markers including caspase-3. Beauchesne does not teach the scFv of FMC63 which binds CD19 and is the scFv of instant SEQ ID NO: 43. Beauchesne does not teach the patient has received two or more prior treatments or ASCT treatment. Beauchesne does not teach the treatment of relapsed or refractory B cell lymphoma, transformed DBLCL, or HGBCL.
These deficiencies are filled by Albertson
Albertson teaches a method of treating a subject having or suspected of having a non-Hodgkin lymphoma (NHL) or relapse or refractory (r/r NHL), the method comprising administering to the subject a dose of T cells comprising T cells expressing an anti-CD19 CAR, wherein: a dose of T cells comprises between at or about 2.5 x 107 – at or about 1 x 108 total CAR expressing T cells (e.g., 25 x 106 – 100 x 106) [claims 28 and 61, para 0215]. Albertson further teaches greater than about 98% of the cells in the composition are T cells (CD3+) [fig. 26, table E15]. Albertson teaches enriched (e.g., at least 80%) naïve-like (Tn) and central memory (Tcm) CAR T cells [0009],[ 0646-0653].
Regarding claim 15, Albertson teaches approximately 20% or fewer CAR T cells in the composition express a marker (Caspase-3) of apoptosis [0908]-[0909] and table E16]. Albertson further teaches the measurement of apoptosis markers to assess the health of the CAR-expressing T cells [0908].
Regarding claims 66-67, Albertson teaches the treatment of subjects with relapsed or refractory lymphoma after treatment with ASCT or two or more previous treatments including CD20 targeted agents and an anthracycline (Claim 56 and [0701]).
Regarding claims 91, 101, 117, and 129-130, Albertson claim 60 teaches an extracellular scFv antigen binding domain (e.g., CD19), a transmembrane domain, a cytoplasmic signaling domain derived from a costimulatory molecule, a cytoplasmic signaling domain derived from a primary signaling ITAM-containing molecule; the CAR comprises, in order, and scFv specific for the antigen (e.g., CD19), a transmembrane domain, a cytoplasmic signaling domain derived from a costimulatory molecule (e.g., 4-1BB), and a cytoplasmic signaling domain derived from a primary signaling ITAM-containing molecule (e.g. CD3-zeta), and optionally further comprises a spacer between the transmembrane domain and the scFv. Albertson claim 60 further teaches the spacer is a polypeptide comprising all or a portion of an Ig hinge or a modified version thereof, the spacer is about 12 amino acids in length (SEQ ID NO: 1), and SEQ ID NO: 2 corresponds to a spacer encoding sequence. Albertson teaches the transmembrane domain is derived from CD28 [0822]. Albertson further teaches an the anti-CD19 FMC63 scFv (SEQ ID NO: 43), CD28 transmembrane domain (SEQ ID NO: 8), 4-1BB costimulatory domain (SEQ ID NO: 12), and CD3-zeta (SEQ ID NO: 14) sequences [claim 60; pgs. 344-346, “Sequences” table].
Regarding claims 120-124, Albertson further teaches embodiments wherein the treated NHL is transformed DLBCL [0692], DLBCL, PMBCL, FL (claim 28 and [0015]), or HGBCL [0095].
Regarding claim 15, it would have been obvious at the time the application was filed to combine the method of preparing CAR T cells for as a therapeutic of Beauchesne with the assessment of CAR expressing T cell viability of measuring caspase-3 taught by Albertson. One of skill in the art would have been motivated to determine the viability of CAR T cells for use as a therapeutic to optimize cells being administered so the patient receives viable CAR T cells that will persist in the patient. There would have been a reasonable expectation of success as the use of standard protocols to measure apoptosis is shown by Albertson to work in CAR-expressing T cells.
It would have been obvious at the time the application was filed to substitute the generic CD19 binding scFv of the CAR of Beauchesne for the CD19 binding scFv of FMC63 of Albertson and to use the method of treatment in the patient population of relapsed/refractory patients B cell lymphoma patients Albertson teaches the treatment of. First, the substitution of the generic CD19 binding scFv of the CAR of Beauchesne with the CD19 binding scFv of FMC63 of Albertson would be a prima facie obvious substitution of a generic for a species art equivalent with the same biologic activity of binding CD19 for use in a CAR for therapeutic applications (see MPEP 2183). Further one of skill in the art would have been motivated to use an art known C19 binding scFv that is taught as effective in the same application of binding CD19 in a CAR for treatment of B cell lymphoma. One of skill in the art would be further motivated to substitute the first line treatment method of Beauchesne with the method of treating relapsed/refractory as taught by Albertson as patients in immediate need for effective treatment. There would have been a reasonable expectation of success as Albertson teaches the FMC63 as an effective scFv in a CAR comprising the same components as Beauchesne for treating relapsed/refractory B cell lymphoma.
Claims 1, 53, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Beauchesna (WO 2018106732 A1) (PTO-892) and Christodoulou et al. (Gene Therapy (2016) 23, 113–118) (Of Record).
Regarding claim 1, Beauchesne teaches a method of genetically engineering cells including into chimeric antigen receptor producing cells (abstract). Beauchesne teaches the cells are CD3+ ([0015]). Beauchesne teaches the administration of 5 x 106 cells to 100 x 106 cells (0423]). Beauchesne teaches the use of T cell subpopulations including ones that are CD27+ and CCR7+ ([0127]) and further teaches central memory T cells which are CD3+, CCR7+, and CD45RA+([0133]), teaching the required cell T subpopulation of the claims. Beauchesne further teaches the enrichment of input cells to 80% or higher ([0350] and claim 18). Beauchesne specifically teaches the input composition that can be at least 80% pure can be memory T cells ([0081]), thus teaching memory T cells that are positive for CD3+, CCR7+, and CD45RA at 80% or higher purity. Beauchesne teaches a target antigen of CD19 ([0053]) and the treatment of non-Hodgkin lymphoma ([0401]-[0402]). Beauchesne teaches embodiments where the cells are not expanded ex vivo or the cells are expanded in vivo ([0038], [0064], [0077], [0087], [00378], [0380]). Beauchesne teaches repeatedly that ex vivo expansion does not need to be done and that in vivo expansion can be done for their genetically modified CAR T cells.
Beauchesne teaches the use of lentiviral vectors (Example 1 and [0543]).
Beauchesne does not teach the integrated vector copy number (iVCN) to total VCN in the CR T cells on average is less than or less than about 0.9 or a diploid genome of about 0.4 per diploid to 3.0 copies per diploid genome.
These deficiencies are filled by Christodoulou.
Christodoulou teaches the measurement of lentiviral vector titer and vector copy number (VCN) as critical to characterization of modified cell products (e.g., CARs) for long-term follow up and the assessment of risk and therapeutic efficiency in patients [title and abstract]. Christodoulou further teaches monitoring iVCN and the ratio to total VCN and/or to diploid genome is an important safety consideration for CAR T cells produced with lentiviral vectors (CAR lentiviral vectors are common in the art) because it is generally understood that higher VCN ratios (e.g., to total VCN or diploid genome) are associated with increased risk of insertional mutagenesis, as evidenced by Christodoulou [introduction]. Christodoulou further teaches that the ‘desired VCN’ is dictated by the required expression, efficacy, long-term stability, and is approximated by application of a specific number of biologically active vector particles to a known number of target cells, and further that the target VCN ratios are optimized for a given ACT [introduction].
It would have been obvious at the time the application was filed to modify the anti-CD19 CAR T cell product characteristics and methods for treating NHL taught by Beauchesne with the iVCN monitoring taught and the CAR T cell safety monitoring (e.g., iVCN to total VCN or diploid genome ratios) methods taught by Christodoulou, in the context of designing and developing a method of treating NHL with anti-CD19 CAR T cells and monitoring associated risks (e.g., insertional mutagenesis). One of ordinary skill in the art would have been motivated to substitute the lentiviral safety monitoring for CAR T cell therapies (e.g., iVCN ratios) as taught by Christodoulou, with Beauchesne’s teachings of lentiviral because Christodoulou further teaches lentiviral produced CAR T cells have an inherent risk of replication-competent virus and insertional mutagenesis, requiring long-term monitoring for the purposes of patient safety. There is a reasonable expectation of success to determine iVCN ratios for lentiviral CAR T cells because Christodoulou teaches iVCN ratio safety monitoring is a common practice in the art for lentiviral CAR T cells due to the risk of insertional mutagenesis. This rationale aligns with the principle simple substitution of one known element for another to obtain predictable results supporting a conclusion of obviousness (see MPEP § 2141(III)).
In regards to the iVCN ratios recited in the instant claim(s) "[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), and see M.P.E.P. § 2144.05(II)(A). Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the target VCN of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine operable and optimal iVCN ratios treatment because the iVCN ratio is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal iVCN ratio of the CAR T cell composition administered to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed iVCN ratio monitoring achieve the same results. It would be conventional and within the skill of the art to determine the optimal iVCN ratios. Accordingly, one can see that the courts, over a period of over 50 years, have consistently held that treatment (e.g., iVCN ratio) optimization is obvious. Therefore, it would have been prima facie obvious to a PHOSITA before the effective filing date of the claimed invention to optimize the iVCN ratio for a lentiviral CAR T cell based on the above teachings of Christodoulou and the courts. There is a reasonable expectation of success for a PHOSITA to optimize iVCN ratios for lentiviral CAR T cells because Christodoulou teaches iVCN ratio optimization as a common practice in the art for lentiviral CAR T cells. This rationale aligns with the principle of optimization within prior art conditions or through routine experimentation, supporting a conclusion of obviousness (see MPEP § 2144.05(II)).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCESCA EDGINGTON-GIORDANO whose telephone number is (571)272-8232. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
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, Julie Wu can be reached at 571-272-5205. 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.
/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
Prosecution Insights