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 .
Claim Rejections - 35 USC § 112(b)
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 4 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 4 is rejected as indefinite because “the target molecule” lacks antecedent basis, rendering the metes and bounds of the claim unclear. For the purposes of examination, claim 4 will be interpreted as being dependent from claim 2.
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.
Claim(s) 1-4, 6, 8-19, 13, 15, and 28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rogers (see instant PTO-892), as evidenced by Awan (see instant PTO-892).
Regarding instant claims 1-4, Rodgers teaches a chimeric antigen receptor – T cell switch molecule (CAR-T switch) comprising a chimeric antigen receptor-interacting domain (CAR-ID), namely the peptide neo-epitope (PNE) from the yeast transcription factor GCN4 (pg. E460, right side, first line), and an antibody targeting moiety, namely the CD19 antibody FMC63 ( pg. E460, right side, likes 10 lines), wherein the targeting moiety specifically binds to the CD19 antigen, which is a target molecule implicated in B-cell malignancies (pg. pg. E460, left side, second paragraph, last four lines). As evidenced by Awan, CD19 is expressed on the cell surface of B-cells in malignancies like leukemia. Regarding claims 1, 6, and 15, Rodgers teaches a complementary CAR-T cell (pg. E461, left side, first line of second paragraph), comprising a 52SR4 single-chain variable fragment (scFv) in the extracellular domain (pg. E461, left side, first two lines) that selectively binds to the GCN4 PNE switch with high affinity (pg. E461, left side, second paragraph). Regarding claims 1-6, 8, 9, and 28, Rodgers teaches a successful method of treating (Figs. 3 and 4) mice with a model of B-cell leukemia (pg. E463, left side, first three lines of second paragraph) by expanding an engineered T cell in vivo (pg. E464, left side, last three lines of first paragraph) by administering a CAR-T switch comprising anti-CD19 targeting moiety and GCN4 PNE CAR-ID (referred to by Rodgers as “CD19 LCNT”) (pg. E463, left side, middle of second paragraph) and a complementary CAR-T cell (Fig. 3 caption). Rogers teaches that the mice that had not previously undergone lymphodepletion (LD) chemotherapy (pg. E467, right side, “Xenograft Mouse Models”). Regarding claims 10 and 13, the CAR-T cells were administered once at the beginning of treatment and the CAR-T switch (i.e. CD19 LCNT) was administered every other day for ten days at a 0.5 mg/kg dose (Fig. 3 caption).
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(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rogers (see instant PTO-892), as applied to claim 6.
Rodgers, as applied to claim 6 above, teaches a method of treating B-cell leukemia by administering a CAR-ID, comprising a GCN4 peptide and an anti-CD19 antibody targeting moiety, and a CAR-T cell comprising an scFv that binds to the CAR-ID to a subject that has not undergone LD chemotherapy.
Rodgers further suggests translating the preclinical results to humans (pg. E466, right side, last paragraph). Rodgers teaches the need for safer CAR-T cell therapy (pg. E459, right side, second paragraph), which their method addresses (pg. E467, left side, second paragraph).
Rodgers does not explicitly teach that the subject is human.
It would be obvious to one of ordinary skill in the art to modify the subject in the method of treating B-cell leukemia by administering a CAR-ID, comprising a GCN4 peptide and an anti-CD19 antibody targeting moiety, and a CAR-T cell comprising an scFv that binds to the CAR-ID to a subject that has not undergone LD chemotherapy of Rodgers, with a human. One of ordinary skill in the art would be motivated to use the method of Rodgers to treat humans because of the explicit suggestion by Rodgers. There would be a reasonable expectation of success because of the successful preclinical results in Rodgers and the enhanced safety of CAR-T cell therapy controlled by a complementary switch.
Claim(s) 6, 15, 16, 21, and 28-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rogers in view of US20190359697A1 (hereafter “Young”; see instant PTO-892).
Rodgers, as applied to claim 6 above, teaches a method of treating B-cell leukemia by administering a CAR-ID, comprising a GCN4 peptide and an anti-CD19 antibody targeting moiety, and a CAR-T cell comprising an scFv that binds to the CAR-ID to a subject that has not undergone LD chemotherapy.
Regarding claim 16, Rodgers does not teach that the GCN4 PNE peptide of the CAR-ID in the switch comprises SEQ ID NO: 1. Regarding claim 21, Rodgers does not teach that the anti-CD19 antibody of the switch comprises light and heavy chain variable regions comprising SEQ ID NOs: 2 and 3, respectively.
Young teaches a chimeric antigen receptor-effector cell switch (hereafter “switch”), wherein the effector cell can be a T cell ([0102]) comprising:
chimeric antigen receptor-interacting domain (CAR-ID) (pg. 114, Claim 209-210) comprising
a GCN4 derivative peptide (pg. 114, Claim 209)
wherein the GCN4 peptide can comprise SEQ ID NO: 154 (pg. 114, Claim 210), which has 100% identity to instant SEQ ID NO: 1 (see below)
and an antibody targeting moiety (pg. 114, Claim 209) that specifically binds to a cell surface target molecule, namely, CD19 ([0007]) in a subject,
wherein the antibody comprises a humanized FMC63 antibody (pg. 114, Claim 209) and can comprise a heavy chain comprising SEQ ID NO: 30, which has 100% identity to instant SEQ ID NO: 3 (see below) and a light chain comprising SEQ ID NO: 7, which has 100% identity to instant SEQ ID NO: 2 (see below) (pg. 114, claims 206 and 211)
Wherein CD19 is implicated in the disease of a subject [0042] such as acute lymphoblastic leukemia [0126].
Young teaches that the CAR-ID of the switch is capable of binding to the scFv in the extracellular domain of a chimeric antigen receptor effector cell (CAR-EC) (pg. 114, claims 200, 213, 214).
It would obvious to combine the GCN4 PNE peptide and anti-CD19 FMC63 antibody of the switch in the method of treating B-cell leukemia in Rodgers, with the GCN4 peptide comprising SEQ ID NO: 154 and humanized FMC63 antibody comprising a heavy chain and light chains of SEQ ID NOs: 30 and 7, respectively, in the method of treating acute lymphoblastic leukemia of Young, to arrive at a method of treating acute lymphoblastic leukemia in a subject that has not undergone lymphodepletion chemotherapy by administering:
a CAR-T switch comprising
a chimeric antigen receptor-interacting domain (CAR-ID) comprising a GCN4 derivative peptide wherein the GCN4 peptide comprises SEQ ID NO: 154, and
an antibody targeting moiety that specifically binds to a cell surface target molecule associated with acute lymphoblastic leukemia, namely CD19, in a subject, comprising a heavy chain comprising SEQ ID NO: 30 and a light chain comprising SEQ ID NO: 7, and
a CAR-T cell comprising an scFv in the extracellular domain that binds the CAR-ID.
One of ordinary skill in the art would be motivated to combine Young and Rodgers because both teach chimeric antigen effector cells and their complementary switches that have the same basic elements, namely a switch comprising a GCN4 peptide and anti-CD19 targeting antibody and a CAR cell comprising an anti-GCN4 scFv. Furthermore, both teach treating the same patient population, namely leukemia patients. There would be a reasonable expectation substituting known sequences, as taught by Young, for the elements of the switch taught by Rodgers. There would be a reasonable expectation of success treating a subject by administering a switch, comprising a GCN4 peptide comprising SEQ ID NO: 154 and anti-CD19 antibody comprising SEQ ID NOs: 30 and 7, and a complementary CAR-T cell because of the successful results taught by Rodgers. In other words, substitution of know sequences for elements in composition known to treat cancer has a reasonable expectation of success.
Instant SEQ ID NO: 1 with 100% identity to SEQ ID NO: 154 of Young
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815
729
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Instant SEQ ID NO: 2 with 100% sequence identity to SEQ ID NO: 30 of Young:
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835
584
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Instant SEQ ID NO: 3 with 100% identity to SEQ ID NO: 7 of Young:
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794
567
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Claim(s) 6, 17 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rogers in view of US20190359697A1 (hereafter “Young”).
Rodgers, as applied to claim 6 above, teaches a method of treating B-cell leukemia by administering a CAR-ID, comprising a GCN4 peptide and an anti-CD19 antibody targeting moiety, and a CAR-T cell comprising an scFv that binds to the CAR-ID to a subject that has not undergone LD chemotherapy.
Regarding claims 17 and 18, Rodgers does not teach that anti-GCN4 scFv of the CAR-T cell comprises SEQ ID NO: 7, or comprises a light chain variable region comprising SEQ ID NO: 4 and heavy chain variable region comprising SEQ ID NO: 5.
Young teaches a chimeric antigen receptor effector cell (CAR-EC) (pg. 114, Claim 215), wherein the CAR-EC can be a T cell ([0101], [0102]), expressing a CAR comprising:
an extracellular domain comprising a single-chain variable fragment (scFv) that binds to the CAR-ID of the switch (pg. 114, claims 200, 213, 214)
wherein the scFv is a humanized anti-GCN4 scFv comprising SEQ ID NO: 322, which has 100% identity to instant SEQ ID NO: 7 and therefore also comprises instant SEQ ID NOs: 4 and 5 (see below) (Claim 200).
It would be obvious to modify the anti-GCN4 scFv in the CAR-T cell in the method of treating leukemia in Rodgers with the anti-GCN4 scFv comprising SEQ ID NO: 322 of Young, (which has 100% sequence identity to instant SEQ ID NO: 7, and which comprises the light and heavy chain variable regions of instant SEQ ID NOs: 4 and 5, respectively) to arrive at a method of treating a tumor in a subject that has not undergone lymphodepletion chemotherapy by administering:
CAR-T switch comprising a GCN4 peptide CAR-ID and an antibody that targets CD19 is present on the surface of a cell and is implicated in leukemia, and
a CAR-T cell comprising an anti-GCN4 scFv comprising SEQ ID NO: 322 that specifically binds the CAR-ID.
One of ordinary skill in the art would be motivated to combine Young and Rodgers because both teach chimeric antigen effector cells and their complementary switches that have the same basic elements, namely a switch comprising a GCN4 peptide and anti-CD19 targeting antibody and a CAR cell comprising an extracellular anti-GCN4 scFv. Furthermore, both treat the same patient population, namely leukemia patients. There would be a reasonable expectation of success treating a subject with leukemia by administering a switch that comprises a GCN4 peptide CAR-ID and an anti-CD19 antibody and a CAR-T cell comprising an anti-GCN4 scFv comprising SEQ ID NO: 322 because of the successful results taught by Rodgers. In other words, substitution of know sequences for elements in composition known to treat cancer has a reasonable expectation of success.
Instant SEQ ID NO: 7 with 100% sequence identity to SEQ ID NO: 322 of Young:
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818
501
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Instant SEQ ID NO: 4 with 100% identity to SEQ ID NO: 322 of Young:
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806
583
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Instant SEQ ID NO: 5 with 100% sequence identity to SEQ ID NO: 322 of Young:
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797
524
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Claim(s) 6 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rogers in view of US20190359697A1 (hereafter “Young”; see instant PTO-892).
Rodgers, as applied to claim 6 above, teaches a method of treating B-cell leukemia by administering a CAR-ID, comprising a GCN4 peptide and an anti-CD19 antibody targeting moiety, and a CAR-T cell comprising an scFv that binds to the CAR-ID to a subject that has not undergone LD chemotherapy.
Regarding instant claim 26, Rodgers does not teach that the CAR of the CAR-T cell is humanized and comprises instant SEQ ID NO: 6.
Young teaches a chimeric antigen receptor effector cell (CAR-EC) (pg. 114, Claim 215), wherein the CAR-EC can be a T cell ([0101], [0102]), expressing a CAR comprising
an extracellular domain comprising a single-chain variable fragment (scFv) that binds to the CAR-ID of the switch (pg. 114, claims 200, 213, 214)
wherein the CAR is humanized comprises SEQ ID NO: 411 which has 100% identity to instant SEQ ID NO: 6 (see below) (pg. 114, claims 200 and 203).
It would be obvious to modify the CAR of the CAR-T cell in the method of treating cancer in Rodgers with SEQ ID NO: 411 of Young to arrive at a method of treating a tumor in a subject that has not undergone lymphodepletion chemotherapy by administering:
CAR-T switch comprising a GCN4 peptide CAR-ID and an antibody that targets CD19 is present on the surface of a cell and is implicated in leukemia, and
A CAR-T cell comprising a CAR that is humanized and comprises SEQ ID NO: 411.
One of ordinary skill would be motivated to combine Young and Rodgers because both teach chimeric antigen effector cells and their complementary switches that have the same basic elements, namely a switch comprising a GCN4 peptide and anti-CD19 targeting antibody and a CAR cell comprising an extracellular anti-GCN4 scFv. There would be a reasonable expectation of success treating a subject with leukemia by administering a switch that comprises a GCN4 peptide CAR-ID and an anti-CD19 antibody and a CAR-T cell comprising that is humanized and comprises SEQ ID NO: 6 because of the successful results taught by Rodgers.
Instant SEQ ID NO: 6 with 100% identity to SEQ ID NO: 411 of Young:
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540
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Claim(s) 6, 11 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rogers in view of US20190359697A1 (hereafter “Young”; see instant PTO-892).
Rodgers, as applied to claim 6 above, teaches a method of treating B-cell leukemia by administering a CAR-ID, comprising a GCN4 peptide and an anti-CD19 antibody targeting moiety, and a CAR-T cell comprising an scFv that binds to the CAR-ID to a subject that has not undergone LD chemotherapy.
Rodgers further teaches optimization of the dosing regimen for switch cells for a given CAR-T cell dose (pg. E464) which impacted the phenotype of CAR-T cells in vivo (pg. E466, right side, second to last paragraph; E465, left side last paragraph).
Regarding claim 11, Rodgers does not explicitly teach that the dose of the CAR-T cells administered to the subject is less than about 1*105 cells per kg of body weight. Regarding claim 12, Rodgers does not teach that the dose of CAR-T cells is less than about 7.5 x 104, 5 x 104, 2.5 x 104, 1 x104, 7.5 x103, 5x103, 2.5 x103, 1 x103, 750, or 500 cells per kg of body weight.
Through routine optimization, it would be obvious for one of ordinary skill in the art to modify the method of treating leukemia by administering 40 × 106 sCAR-T cells to arrive at method of treating leukemia by administering less than about 7.5 x 104 sCAR-T cells which comprise a GCN4 scFv and a switch comprising a GCN4 peptide CAR-ID and an anti-CD19 targeting moiety that binds to CD19 cells associated with leukemia. Rodgers teaches that the dosage of the switch consequently impacts the activity, phenotype and number of CAR-T cells; thus, it would be obvious to optimize the initial dose of the CAR-T cells in response to optimization of the switch dose. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of CAR-T cells to dose a subject, as well as the safe and optimal dosing schedule needed to achieve the desired results, because Rodgers teaches adjusting the dosing regimen of the complementary switch.
MPEP §§ 2144.05 states: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA1955)).
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 1-4, 6-9, 10, 13, 15, 21, 26, 28, and 29, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/715,941 (hereafter “reference application”) in view of Rodgers.
Regarding instant claims 1-4, 6-9, 21, 26, 28, and 29, Claim 1 of the reference application teach a method of treating a CD19- positive malignancy in a human subject comprising administering to the subject (a) a chimeric antigen receptor - T cell switch molecule (CAR-T switch) comprising an anti- CD19 Fab antibody that comprises a light chain variable region and a heavy chain variable region sequence set forth as SEQ ID NOs:2 and 3, respectively, and (b) a complementary CAR-T cell comprising a CAR sequence set forth in SEQ ID NO:6; thereby treating, arresting growth of, and/or promoting regression of, the B cell malignancy in the subject. SEQ ID NOs: 2, 3, and 6 of the reference application are identical to instant SEQ ID NOs: 2, 3, and 6. Regarding instant claims 10, claims 3 and 4 of the reference application teach that the subject is administered with one dose of the CAR-T cell at the beginning of the treatment, and multiple doses of the CAR-T switch during the course of the treatment. Regarding instant claim 13, claim 9-12 of the reference application teach that the dose of the switch is 0.06 mg per kg of body weight. Regarding instant claim 29, claims 15 and 22 of the reference application teach treating chronic lymphocytic leukemia.
The reference application does not teach that the subject has not undergone lymphodepletion chemotherapy. The reference application does not teach that the switch further comprises a CAR-ID.
The teachings of Rodgers are above.
It would be obvious to combine the method of treating chronic lymphocytic leukemia (CLL) by administering a CAR-T cell and complementary switch of the reference application, with the:
Leukemia patient population that has not undergone lymphodepletion chemotherapy,
CAR-T switch comprising a CAR-ID comprising a GCN4 derivative peptide and an anti-CD19 targeting antibody
CAR-T cell comprising a CAR extracellular domain that comprises an ant-GCN4 scFv
as taught by Rodgers, to arrive at a method of treating the CLL patient population that has not undergone lymphodepletion by administering:
A switch at dose of 0.06 mg per kg of body weight comprising
CAR-ID comprising a GCN4 derivative peptide
anti- CD19 Fab antibody that comprises a light chain variable region and a heavy chain variable region sequence set forth as SEQ ID NOs: 2 and 3, respectively and
A CAR-T cell comprising a
A CAR extracellular domain comprising an anti-GCN4 scFv
CAR sequence set forth in SEQ ID NO: 6, which necessarily requires that it is humanized
wherein the subject is administered with one dose of the CAR-T cell at the beginning of the treatment, and multiple doses of the CAR-T switch during the course of the treatment. One of ordinary skill would be motivated to combine the teachings of the reference application and Rodgers because both sources teach treating individuals with a CD19 malignancy with a complementary CAR-T cell and a switch comprising an anti-CD19 antibody. There would be a reasonable expectation of success using a known method, namely the CAR-T cell and switch of the reference application, with a population known to benefit from this therapy, namely leukemia subjects that have not undergone lymphodepletion chemotherapy.
Regarding instant claims 1-4, while the modified method of the reference application and Rodgers does not explicitly teach expanding an engineered T cell in a subject, the modified method would necessarily require this, as taught by Rodgers, and because the active method steps of instant claims 1-4 are anticipated by the modified method.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 6-10, 13, 15, 17-18, 21, 26, 28 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of copending Application No. 17/461,365 in view of Rodgers.
Regarding instant claims 1-4, 6, claim 14 of the reference application teach a method of treating a subject with a CD19 positive disease by administering a chimeric antigen receptor-effector cell (CAR-EC) platform; Claims 1, 2, 3, and 12 of the reference application teach that the CAR-EC platform can include a CAR-T cell wherein the CAR is humanized and comprises an anti-GCN4 scFv comprising SEQ ID NO: 322 (which is identical to instant SEQ ID NO: 7) as well as a CAR-EC switch that comprises a CAR-ID comprising a GCN4 derivative peptide of SEQ ID NO: 26, (which is identical to instant SEQ ID NO: 1) that interacts with the anti-GCN scFv in the chimeric antigen receptor of the CAR-EC and a humanized targeting antibody comprising SEQ ID NOs: 30 and 7, which are identical to instant SEQ ID NOs: 2 and 3, respectively recited in instant claim 21. Regarding instant claim 26, claim 4 of the reference application further teaches that the CAR comprises SEQ ID NO: 411, which is identical to instant SEQ ID NO: 6.
The method of the reference application does not teach that the subject treated has not undergone lymphodepletion chemotherapy or is human.
The teachings of Rodgers are above. Rodgers further teaches that the greatest success of in CAR-T cell therapy targeting CD19 has been in acute lymphoblastic leukemia (ALL) (pg.E459, left side, first paragraph).
It would be obvious to one of ordinary skill in the art to combine the method of treating a subject with a CD19 positive disease by administration of a CAR-T cell and complementary switch of the reference application with
Subject is a human that has ALL but has not undergone lymphodepletion chemotherapy, and
Administering to the subject a single dose of CAR-T cell at the beginning of treatment and multiple doses of CAR-T switch during the course of treatment, wherein the dose of the switch is about 0.5mg per kg of body weight
Wherein the switch comprises both a CAR-ID comprising a GCN4 derivative peptide and a CD19 antibody
of Rodgers to arrive at a method of treating ALL in a human that has not undergone lymphodepletion chemotherapy by
Administering a CAR-T cell comprising a humanized anti-GCN4 scFv comprising SEQ ID NO: 411 (which is identical to instant SEQ ID NO: 6) and comprises SEQ ID NO: 322 (which is identical to instant SEQ ID NO: 7 and therefore comprises instant SEQ ID NOs: 4 and 5) at a single dose of 0.5mg/kg of body weight and
Administering multiple doses of switch during the course of treatment wherein the switch comprises a CAR-ID comprising a GCN4 derivative peptide of SEQ ID NO: 26 and an anti-CD19 antibody comprising SEQ ID NOs: 30 and 7.
One of ordinary skill would be motivated to combine the teachings of the reference application and Rodgers because both sources teach treating individuals with a CD19 malignancy with a complementary CAR-T cell and a switch comprising an anti-CD19 antibody. There would be a reasonable expectation of success using a known method, namely the CAR-T cell and switch of the reference application, with a population known to benefit from this therapy, namely leukemia subjects that have not undergone lymphodepletion chemotherapy, as demonstrated by Rodgers.
Regarding instant claims 1-4, the modified method of the reference application and Rodgers necessarily requires expansion of the engineered T-cell in the subject, as taught by Rodgers.
This is a provisional nonstatutory double patenting rejection.
Claims 6, 11, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of copending Application No. 17/461,365 in view of Rodgers.
The modified method of the reference application and Rodgers teach a method
of treat method of treating leukemia in a human that has not undergone lymphodepletion chemotherapy by
Administering a CAR-T cell comprising a humanized anti-GCN4 scFv comprising SEQ ID NO: 411 (which is identical to instant SEQ ID NO: 6) and comprises SEQ ID NO: 322 (which is identical to instant SEQ ID NO: 7 and therefore comprises instant SEQ ID NOs: 4 and 5) at a single dose of 0.5mg/kg of body weight and
Administering multiple doses of switch during the course of treatment that comprises a GCN4 derivative peptide of SEQ ID NO: 26 and an anti-CD19 antibody comprising SEQ ID NOs: 30 and 7.
The modified method of the reference application and Rodgers does not teach that the CAR-T cells are administered at a dose of less than about 7.5*104 cells per kg of weight.
The teachings of Rodgers are above.
Through routine optimization, it would be obvious to modify the dose of the CAR-T cells in the modified method of the reference application and Rodgers with a dose of less than about 7.5*104 cells per kg of body weight. Rodgers teaches that the dosage of the switch consequently impacts the activity, phenotype and number of CAR-T cells; thus it would be obvious to optimize the initial dose of the CAR-T cells in response to optimization of the switch dose. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of CAR-T cells to dose a subject, as well as the safe and optimal dosing schedule needed to achieve the desired results, because Rodgers teaches adjusting the dosing regimen of the complementary switch.
MPEP §§ 2144.05 states: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages," (see In re Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382). 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," (See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA1955)).
This is a provisional nonstatutory double patenting rejection
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE C BUCCINI whose telephone number is (571)272-1352. The examiner can normally be reached M-F 7:30-5 EST.
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, Jeffrey Stucker can be reached at 5712720911. 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.
/MICHELLE CALLAHAN BUCCINI/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
Prosecution Insights