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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 September 1, 2026 has been entered. By way of this submission, Applicant has amended claims 1 and 15 and cancelled claims 13, 14, and 16.
Claims 1-5, 7-11, 15, 18-22 and 25 are pending in the application. Claims 9, 11, 18, and 25 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed May 27, 2025.
Claims 1-5, 7-8, 10, 15, and 19-22 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated May 21, 2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 1, 2026 was filed after the mailing date of the first Office action on the merits on January 6, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Claims 1-5 and 15 were previously rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by June (US20150283178A1).
Applicant argues that June does not anticipate every aspect of the claims as amended; specifically, June does not teach CD4+ and CD8+ CAR T cells prepared from peripheral blood mononuclear cells (PBMCs) by positive selection for CD4+ and CD8+ cells and partial or complete depletion of circulating cancer cells.
Applicant's arguments have been considered but are not found persuasive.
June teaches enrichment of cells for CD4+ and CD8+ T cells by positive selection with anti-CD3 and anti-CD28 and IL-2. (para. 0456: "Methods described herein can include a positive selection step. For example, T cells can isolated by incubation with anti-CD3/anti-CD28 (e.g., 3×28)-conjugated beads..."; para. 0518: "Conditions appropriate for T cell culture include an appropriate media ... that may contain factors necessary for proliferation and viability, including serum (e.g., fetal bovine or human serum), interleukin-2 (IL-2)..."). Because these antigens are typically exclusively expressed by T cells, performing the protocol described in June would therefore exclude selection of CD19+ tumor cells such as MCL cells which do not express the antigen. Therefore, circulating tumor cells would be "depleted" at least partially by following the protocol of June.
June further teaches that PBMCs may be transduced with lentiviral vectors containing a nucleic acid encoding the CAR (para. 0826, 0940, 0968, and 0990).
This rejection is therefore maintained.
Claims 7-8, 10, and 19-22 were previously rejected under 35 U.S.C. 103 as being unpatentable over June as applied to claim 1 above, and further in view of Gore (Blood Cancer J. 2018 Aug 22;8(9):80), Kansagra (Bone Marrow Transplant. 2019 Nov;54(11): 868-1880), Paul (Symposium on neoplastic hematology and medical oncology, Volume 91, Issue 11 p1645-1666 November 2016), and Better (US20150344844A1).
Applicant argues that the products used in the claimed method are distinguishable from the products used in June, as June describes a CAR with a 4-1BB intracellular signaling domain (CTL-019, also known as tisagenlecleucel), whereas the claimed method uses a CAR with a CD28 intracellular signaling region (KTE-X19, also known as brexucabtagene autoleucel). Applicant further argues that in Minson (cited by Applicant previously in an IDS), tisagenlecleucel was used in combination with ibrutinib to achieve treatment of mantle cell lymphoma, whereas KTE-X19 was used alone, and the results of KTE-X19 in treating MCL alone were unexpected.
Applicant's arguments have been considered but are not found persuasive.
June teaches that the "intracellular signaling domain of the CAR can comprise the CD3-zeta signaling domain by itself or it can be combined with any other desired intracellular signaling domain(s) useful in the context of a CAR", which includes both CD28 and 4-1BB (para. 0344). This is a suggestion to use CD28 in CAR for treatment of MCL.
Additionally, Guedan (cited by Applicant previously in an IDS) teaches that "CD28 and 4-1BB are the most widely used costimulatory endodomains in CARs. Clinical trials with CARs incorporating CD28 or 4-1BB intracellular domains showed similar response rates in patients with hematologic malignancies." (page 147, right column, last paragraph). While Guedan goes on to describe the functional differences between CD28 and 4-1BB, it was known that they performed a similar function, and both domains resulted in a functional CAR. Guedan also suggests means by which the skilled artisan could choose which domain to use (page 148, left column, first paragraph: "The high effector function and self-limited expansion of CD28-based CARs may be ideal to transiently treat diseases with a rapid tumor elimination and short-term persistence of the CAR (i.e., as a bridge therapy for allogeneic hematopoietic stem cell transplantation). By contrast, 4-1BB-based CARs may be used to treat diseases in which complete responses require sustained T cell persistence.").
The teachings of Guedan make it clear that one of ordinary skill would know whether to use CD28 or 4-1BB in order to treat varying types of cancer, with a predictable expectation of success.
Applicant's arguments are also inconsistent, as Applicant had previously argued in the reply dated April 3, 2026 at page 10 that the subject matter of Minson was comparable to that of the instant claims. Applicant also does not bring up treatment with ibrutinib in this context. It is also noted that prior treatment with ibrutinib is within the scope of the claims.
This rejection is therefore maintained.
Claims 1-5, 7-8, 10, 15, and 19-22, were previously rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 12,156,887 in view of June, Gore, Kansagra, Paul, and Better.
Applicant has requested to hold this rejection in abeyance until allowable claims are identified. As no claims are currently allowable, this rejection is therefore maintained.
Claims 1-5 and 15 were previously provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, and 10 of copending Application No. 17/091,039 (reference application).
Application 17/091,039 has issued as U.S. patent 12,600,775. This provisional rejection is therefore withdrawn.
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.
(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 1-5 and 15 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by June (US20150283178A1).
June teaches a method of treating a B cell malignancy, comprising administering T cells expressing an anti-CD19 chimeric antigen receptor (CAR) (para. 0006). June further teaches that the B cell malignancy may be B-cell acute lymphoid leukemia (B-ALL) (para. 0008), and that the cells administered are autologous (para. 0030 and 0034). June also teaches the use of the FMC63 scFv (para. 0306).
June teaches enrichment of cells for CD4+ and CD8+ T cells by positive selection with anti-CD3 and anti-CD28 in the presence of IL-2. (para. 0456: "Methods described herein can include a positive selection step. For example, T cells can be isolated by incubation with anti-CD3/anti-CD28 (e.g., 3×28)-conjugated beads..."; para. 0518: "Conditions appropriate for T cell culture include an appropriate media ... that may contain factors necessary for proliferation and viability, including serum (e.g., fetal bovine or human serum), interleukin-2 (IL-2)..."). Because these antigens are typically exclusively expressed by T cells, performing the protocol described in June would therefore exclude selection of CD19+ tumor cells such as MCL cells which do not express the antigen. Therefore, circulating tumor cells would be "depleted" at least partially by following the protocol of June.
June further teaches that PBMCs may be transduced with lentiviral vectors containing a nucleic acid encoding the CAR (para. 0826, 0940, 0968, and 0990).
June further teaches that the patient has relapsed after one or more other therapies, such as the BTK inhibitor ibrutinib (para. 0062), which is pertinent to claims 2-5. June also teaches patients who are relapsed may have had 1-4 prior cancer therapies (para. 0545).
While June does not explicitly teach that the T cell product comprises fewer cancer cells than a T cell product comprising T cells from a leukapheresis product that has not been positively selected for CD4+ and CD8+ T cells, the method of June is identical to the instantly claimed method and would therefore result in a product with identical features. June therefore inherently anticipates the subject matter of claim 15. MPEP 2112.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7-8, 10, 19, 20-22, and 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over June as applied to claim 1 above, and further in view of Gore (Blood Cancer J. 2018 Aug 22;8(9):80), Kansagra (Bone Marrow Transplant. 2019 Nov;54(11): 868-1880), and Better (US20150344844A1).
The teachings of June have been discussed supra. However, June does not teach blinatumomab, bridging therapy after leukapheresis and before conditioning/lymphodepleting chemotherapy, or FMC63-28Z.
Gore teaches CAR-T cell treatment with an anti-CD19 CAR-T cell treatment in CD19-positive patients with B-cell ALL after prior treatment with blinatumomab (page 6, right column, third paragraph).
Kansagra teaches bridging chemotherapy after T-cell collection by leukapheresis and prior to lymphodepleting chemotherapy, prior to anti-CD19 therapy for patients with B-cell ALL (page 1871).
Kansagra further teaches lymphodepleting chemotherapy of fludarabine and cyclophosphamide (page 1872, left column, first paragraph), which is pertinent to claim 10.
Better teaches an anti-CD19 CAR made with FMC63-28Z and the retroviral vector MSGV, which is replication incompetent (para. 0004 and 0026).
Better further teaches activating CAR-T cells with anti-CD3 antibodies, anti-CD28 antibodies, and IL-2 (para. 0034).
Better further teaches administering one or more doses of the cells to the subject (para. 0007 and 0134).
Better also teaches that an attending physician can determine appropriate dosages of treatments suitable for treatment (para. 0132 and 0309).
Better further teaches that a complete response to treatment can be measured by the Lugano criteria (para. 0030 and 0171), which is pertinent to claim 19.
Better further teaches that treatment with CAR-T cells may result in cytokine release syndrome and neurotoxicity (i.e., neurologic toxicity) within a week (para. 0177-0178), which is pertinent to claims 20 and 21.
Better further teaches that cytokine release syndrome may present as fever, chills, fatigue, tachycardia, nausea, hypoxia, and hypotension, and neurological complications include seizure, encephalopathy, aphasia (i.e., speech disorders), delirium (i.e., confusion), and seizure-like activity (i.e. tremors)(para. 0183), which is pertinent to claim 22.
Better further teaches tocilizumab for treatment of cytokine release syndrome (para. 0181).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of June, Gore, Kansagra, Paul, and Better to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of the references are concerned with treatment for B-cell ALL. Starting from the treatment of June, additional features of suitable treatment such as prior treatment with blinatumomab, bridging chemotherapy, and treatment of neurotoxicity were also known according to Gore, Kansagra, and Better, respectively. The features of Gore, Kansagra, Paul, and Better for the treatment of B-cell ALL could be applied to the treatment of June through known methods, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
The difference between the claimed invention and the prior art is the schedules and dosages of the treatments. However, it is noted that determination of dosage is routinely determined by the ordinary artisan as of the effective filing date of the claimed invention, and was known as a result effective variable that depends on the conditions of the patients. 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) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). This is especially true as Better teaches that an attending physician can determine appropriate dosages of treatments suitable for treatment (para. 0132 and 0309). One of ordinary skill in the art would appreciate the timing or dosage of the therapy could be adjusted to achieve optimum therapeutic efficacy.
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 1-5, 7-8, 10, 15, and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 12,156,887 in view of June, Gore, Kansagra, and Better.
The '887 patent claims a method of treating a malignancy by administering an effective dose of anti-CD19 chimeric antigen receptor (CAR)-T cells to the patient (claim 1).
The '887 patent further claims the malignancy is B-cell acute lymphoid leukemia (B-ALL)(claim 5).
However, the '887 patent does not claim autologous cells, blinatumomab, or bridging therapy after leukapheresis and before conditioning/lymphodepleting chemotherapy.
June teaches a method of treating a B cell malignancy, comprising administering T cells expressing an anti-CD19 chimeric antigen receptor (CAR) (para. 0006). June further teaches that the B cell malignancy may be B-cell acute lymphoid leukemia (B-ALL) (para. 0008), and that the cells administered are autologous (para. 0030 and 0034). June also teaches the use of the FMC63 scFv (para. 0306).
June teaches enrichment of cells for CD4+ and CD8+ T cells by positive selection with anti-CD3 and anti-CD28 in the presence of IL-2. (para. 0456: "Methods described herein can include a positive selection step. For example, T cells can be isolated by incubation with anti-CD3/anti-CD28 (e.g., 3×28)-conjugated beads..."; para. 0518: "Conditions appropriate for T cell culture include an appropriate media ... that may contain factors necessary for proliferation and viability, including serum (e.g., fetal bovine or human serum), interleukin-2 (IL-2)..."). Because these antigens are typically exclusively expressed by T cells, performing the protocol described in June would therefore exclude selection of CD19+ tumor cells such as MCL cells which do not express the antigen. Therefore, circulating tumor cells would be "depleted" at least partially by following the protocol of June.
June further teaches that PBMCs may be transduced with lentiviral vectors containing a nucleic acid encoding the CAR (para. 0826, 0940, 0968, and 0990).
June further teaches that the patient has relapsed after one or more other therapies, such as the BTK inhibitor ibrutinib (para. 0062), which is pertinent to claims 2-5. June also teaches patients who are relapsed may have had 1-4 prior cancer therapies (para. 0545).
While June does not explicitly teach that the T cell product comprises fewer cancer cells than a T cell product comprising T cells from a leukapheresis product that has not been positively selected for CD4+ and CD8+ T cells, the method of June is identical to the instantly claimed method and would therefore result in a product with identical features. June therefore inherently anticipates the subject matter of claim 15. MPEP 2112.
Gore teaches CAR-T cell treatment with an anti-CD19 CAR-T cell treatment in CD19-positive patients with B-cell ALL after prior treatment with blinatumomab (page 6, right column, third paragraph).
Kansagra teaches bridging chemotherapy after T-cell collection by leukapheresis and prior to lymphodepleting chemotherapy, prior to anti-CD19 therapy for patients with B-cell ALL (page 1871).
Kansagra further teaches lymphodepleting chemotherapy of fludarabine and cyclophosphamide (page 1872, left column, first paragraph), which is pertinent to claim 10.
Better teaches an anti-CD19 CAR made with FMC63-28Z and the retroviral vector MSGV, which is replication incompetent (para. 0004 and 0026).
Better further teaches activating CAR-T cells with anti-CD3 antibodies, anti-CD28 antibodies, and IL-2 (para. 0034).
Better further teaches administering one or more doses of the cells to the subject (para. 0007 and 0134).
Better also teaches that an attending physician can determine appropriate dosages of treatments suitable for treatment (para. 0132 and 0309).
Better further teaches that a complete response to treatment can be measured by the Lugano criteria (para. 0030 and 0171), which is pertinent to claim 19.
Better further teaches that treatment with CAR-T cells may result in cytokine release syndrome and neurotoxicity (i.e., neurologic toxicity) within a week (para. 0177-0178), which is pertinent to claims 20 and 21.
Better further teaches that cytokine release syndrome may present as fever, chills, fatigue, tachycardia, nausea, hypoxia, and hypotension, and neurological complications include seizure, encephalopathy, aphasia (i.e., speech disorders), delirium (i.e., confusion), and seizure-like activity (i.e. tremors)(para. 0183), which is pertinent to claim 22.
Better further teaches tocilizumab for treatment of cytokine release syndrome (para. 0181).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the '887 patent with teachings of June, Gore, Kansagra, Paul, and Better to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of the references are concerned with treatment for B-cell ALL. Starting from the treatment of June, additional features of suitable treatment such as prior treatment with blinatumomab, bridging chemotherapy, and treatment of neurotoxicity were also known according to Gore, Kansagra, Paul, and Better, respectively. The features of Gore, Kansagra, Paul, and Better for the treatment of B-cell ALL could be applied to the treatment of June and the '887 patent through known methods, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
The difference between the claimed invention and the prior art is the schedules and dosages of the treatments. However, it is noted that determination of dosage is routinely determined by the ordinary artisan as of the effective filing date of the claimed invention, and was known as a result effective variable that depends on the conditions of the patients. 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) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). This is especially true as Better teaches that an attending physician can determine appropriate dosages of treatments suitable for treatment (para. 0132 and 0309). One of ordinary skill in the art would appreciate the timing or dosage of the therapy could be adjusted to achieve optimum therapeutic efficacy.
Claims 1-5, 8, 15, and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-9 of U.S. Patent No. 12,600,775 in view of Better. This is a new grounds of rejection.
The '775 patent claims a method of treating relapsed or refractory mantle cell lymphoma (MCL) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition which comprises autologous T cells expressing an anti-CD19 chimeric antigen receptor (CAR) wherein the T cells comprise CD4+ and CD8+ CAR T cells that are prepared from peripheral blood mononuclear cells (PBMCs) by positive enrichment and partial or complete depletion of circulating cancer cells and wherein the anti-CD19 CAR comprises an anti-CD19 single-chain variable fragment (scFv) comprising the heavy chain and light chain variable regions of FMC63, a CD28 intracellular signaling region, and a CD3-zeta signaling domain (claim 1).
The '775 patent further claims that the MCL is refractory to, or has relapsed following, one or more of chemotherapy, radiotherapy, immunotherapy, an autologous stem cell transplant, or any combination thereof (claim 2).
The '775 patent further claims that the subject has received 1-5 prior treatments, and the prior treatment may be a Bruton Tyrosine Kinase inhibitor (BTKi) (claim 3).
The '775 patent further claims that the BTKi is ibrutinib (claim 4).
The '775 patent further claims that the subject receives a bridging therapy after leukapheresis to obtain the PBMCs and before the consequent partial or complete depletion of circulating cancer cells (claim 5).
The '775 patent further claims that the PBMC are enriched for T cells by selection for CD4+ and CD8+ cells, activated with anti-CD3 and anti-CD28 antibodies in the presence of IL-2, and then transduced with a replication-incompetent viral vector containing a polynucleotide encoding the anti-CD19 CAR (claim 8).
While the '775 patent does not explicitly claim that the T cell product comprises fewer cancer cells than a T cell product comprising T cells from a leukapheresis product that has not been positively selected for CD4+ and CD8+ T cells, the method of the '775 patent is identical to the instantly claimed method and would therefore result in a product with identical features. The '775 patent therefore inherently anticipates the subject matter of claim 15. MPEP 2112.
However, the '775 patent does not teach the Lugano classification or cytokine release syndrome.
Better teaches an anti-CD19 CAR made with FMC63-28Z and the retroviral vector MSGV, which is replication incompetent (para. 0004 and 0026).
Better further teaches activating CAR-T cells with anti-CD3 antibodies, anti-CD28 antibodies, and IL-2 (para. 0034).
Better further teaches administering one or more doses of the cells to the subject (para. 0007 and 0134).
Better also teaches that an attending physician can determine appropriate dosages of treatments suitable for treatment (para. 0132 and 0309).
Better further teaches that a complete response to treatment can be measured by the Lugano criteria (para. 0030 and 0171), which is pertinent to claim 19.
Better further teaches that treatment with CAR-T cells may result in cytokine release syndrome and neurotoxicity (i.e., neurologic toxicity) within a week (para. 0177-0178), which is pertinent to claims 20 and 21.
Better further teaches that cytokine release syndrome may present as fever, chills, fatigue, tachycardia, nausea, hypoxia, and hypotension, and neurological complications include seizure, encephalopathy, aphasia (i.e., speech disorders), delirium (i.e., confusion), and seizure-like activity (i.e. tremors)(para. 0183), which is pertinent to claim 22.
Better also teaches treatment of mantle cell lymphoma (para. 0055).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the '775 patent with the teachings of Better to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both the '775 patent and Better are concerned with treatment for MCL. Starting from the treatment of the '775 patent, additional features of suitable treatment such as evaluation of neurotoxicity were also known according to Better. The features of Better for the treatment of MCL could be applied to the treatment of the '775 patent through known methods, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
The difference between the claimed invention and the prior art is the schedules and dosages of the treatments. However, it is noted that determination of dosage is routinely determined by the ordinary artisan as of the effective filing date of the claimed invention, and was known as a result effective variable that depends on the conditions of the patients. 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) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). This is especially true as Better teaches that an attending physician can determine appropriate dosages of treatments suitable for treatment (para. 0132 and 0309). One of ordinary skill in the art would appreciate the timing or dosage of the therapy could be adjusted to achieve optimum therapeutic efficacy.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Bedoya (US20160185861A1) teaches that anti-CD19 CAR-T cells are useful for treatment of B-cell acute lymphoid leukemia and mantle cell lymphoma (para. 0057). Bedoya also teaches that the anti-CD19 CAR-T treatment is CTL-019, also known as tisagenlecleucel (para. 0282).
Brogdon (US20140271635A1) teaches that anti-CD19 CAR-T cells are useful for treatment of B-cell acute lymphoid leukemia and mantle cell lymphoma (para. 0035-0036). Brogdon further teaches isolation of T cells from PBMC by positive selection with anti-CD3 and anti-CD28 (para. 0269). Brogdon further teaches the anti-CD19 FMC63 scFv (para. 0154).
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 6:00 to 2:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1644
