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 .
Election/Restrictions
Applicant has previously elected without traverse Group I, claims 1-8, 10-22, and 27-29, drawn to a composition comprising a first polypeptide and a second polypeptide, wherein the first polypeptide comprises :a) a first leader sequence; b) an scFv that binds to CD19; c) a CD8a hinge domain; d) a CD8a transmembrane domain; e) a 4-1BB intracellular signaling sequence; and f) a CD3 intracellular T cell signaling sequence; and wherein the second polypeptide comprises: a) a second leader sequence; b) an scFv that binds to FLT3; c) a CD8a hinge domain; d) a CD8a transmembrane domain; e) a 4 -1BB intracellular signaling sequence; and f) a CD3 intracellular T cell
signaling sequence, an expression construct comprising a nucleotide sequence encoding the first polypeptide and the
second polypeptide of the composition, and a host cell comprising the composition, in the reply filed on 10/31/2025.
Applicants have also previously cancelled non-elected Groups II-IV, drawn to claims 23-26, 30-35, 39-40, and 36-38, respectively.
Applicants have also previously elected from species Group A b. a composition comprising a first polypeptide and a second polypeptide, wherein the first polypeptide comprises :a) a first leader sequence; b) an scFv that binds to CD19; c) a CD8a hinge domain; d) a CD8a transmembrane domain; e) a 4-1BB intracellular signaling sequence; and f) a CD3 intracellular T cell signaling sequence; and wherein the second polypeptide comprises: a) a second leader sequence; b) an scFv that binds to FLT3; c) a CD8a hinge domain; d) a CD8a transmembrane domain; e) a 4-1BB intracellular signaling sequence; and f) a CD3 intracellular T cell signaling sequence, from species Group B a. the amino acid sequences SEQ ID NO: 33, SEQ ID NO: 67, and SEQ ID NO: 34 of the ScFv that binds to CD19, from species Group C a. the amino acid sequence SEQ ID NO: 74 of the CD3 ζ intracellular T cell signaling sequence, from species Group D c. the amino acid sequence SEQ ID NO: 18 of the ScFv that binds to FLT3, from species Group E b. the amino acid sequence SEQ ID NO: 151 of the first polypeptide, and from species Group F b. the amino acid sequence SEQ ID NO: 152 of the second polypeptide.
It is further noted that the election of species requirement of all the species groups was previously withdrawn. All species have been considered on the merits.
Claims 1- 8, 10-22, and 27-29 were previously pending. Claims 1-21, 23-26, and 30-40 are cancelled. Claim 22, 27-29 are currently pending and under examination in the instant application.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 28-29 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter:
Applicants’ amendments, filed 05/04/2026 overcome the 35 U.S.C. 101 rejection. Applicants have specifically amended claim 28-29 to be “method” claims instead of “use” claims, so that it falls within at least one of the four categories of patent eligible subject matter and to comply with 35 U.S.C. 101. The rejection is therefore withdrawn.
RE: Rejection of claims 28-29 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph:
Applicants’ amendments, filed 05/04/2026 overcome the 35 U.S.C. 101 rejection. Applicants have specifically amended claim 28-29 to be “method” claims instead of “use” claims, such that it claims a clear process with setting forth the required steps in at least independent claim 28. The rejection is therefore withdrawn.
RE: Rejection of claims 1-2, 5-8, 12-14, 19-22, and 27-29 under 35 U.S.C. 102(a)(1) and (a)(2) as being
anticipated by Bitter et al. (US10253086B2):
Applicants’ amendments, filed 05/04/2026 overcome the 35 U.S.C. 102(a)(1) and (a)(2) rejection. Applicants have specifically cancelled all claims 1-2, 5-8, 12-14, 19-21 and amended claims 22, 27-29 so that at least independent claims 22 and 27 to recite the new limitation “a self-cleaving linker peptide comprising the amino acid sequence set forth in SEQ ID NO: 125”. The rejection is therefore withdrawn. However, in view of applicants’ amendments, a new rejection is made in view of QIN et al.
RE: Rejection of claims 1-4 under 35 U.S.C. 103 as being unpatentable over Bitter et al. (US10253086B2), in view of Stephan et al. (US20160145348A1):
Applicants’ amendments, filed 05/04/2026 overcome the 35 U.S.C. 103 rejection. Applicants have specifically cancelled claims 1-4. The rejection is therefore moot.
RE: Rejection of claims 1-2 and 10-11 under 35 U.S.C. 103 as being unpatentable over Bitter et al. (US10253086B2), in view of Chien et al. (US12202902B2):
Applicants’ amendments, filed 05/04/2026 overcome the 35 U.S.C. 103 rejection. Applicants have specifically cancelled claims 1-2 and 10-11. The rejection is therefore moot.
RE: Rejection of claims 1-2 and 15-18 under 35 U.S.C. 103 as being unpatentable over Bitter et al. (US10253086B2), in view of Stephan et al. (US20160145348A1) and Chien et al. (US12202902B2):
Applicants’ amendments, filed 05/04/2026 overcome the 35 U.S.C. 103 rejection. Applicants have specifically cancelled claims 1-2 and 15-18. The rejection is therefore moot.
New/Maintained Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 22, 27-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bitter et al. (US10253086B2, filed on 04/08/2016, and published on 04/09/2019), in view of QIN et al. (WO2018213337A1, filed on 05/15/2018, and published on 11/22/2018).
Regarding claim 22, Bitter et al. teaches a population of T cells comprising a nucleotide sequence encoding a first polypeptide and a nucleotide sequence encoding a second polypeptide (column 13, lines 1-4, column 12, lines 14-20). Bitter et al. further teaches a composition comprising: (i) a first nucleic acid encoding, or a first polypeptide comprising a CAR molecule that binds CD19 and (ii) a second nucleic acid encoding, or a second polypeptide comprising a CAR molecule that binds a B-cell antigen, such as FLT-3 (Column 12, lines 20-26). Bitter et al. further teaches that the CD19 CAR comprises an scFv (column 28, lines 18-20), a CD28 hinge, a CD28 transmembrane domain (column 29, lines 55-62), CD28 intracellular signaling domain described herein and/or a CD3 zeta intracellular T cell signaling domain (column 17, lines 50-55). Bitter et al. further teaches that the FLT-3 CAR comprises an scFv, a CD8a hinge, a CD8a transmembrane domain (column 114, lines 7-19), 4-1BB intracellular signaling domain described herein and/or a CD3 zeta intracellular T cell signaling domain (column 21, lines 30-36). Bitter et al. also teaches that the nucleotide sequence encoding said first polypeptide is joined to said nucleotide sequence encoding said second polypeptide by a nucleotide sequence encoding a self-cleaving linker peptide (column 74, lines 20-24, column 145, lines 39-41, and column 75, lines 38-47).
However, Bitter et al. fails to teach that the self-cleaving linker peptide comprises the amino acid sequence set forth in instant SEQ ID NO: 125.
However, QIN et al. teaches SEQ ID NO: 52 of the anti-CD 19/anti-CD22 V8 CAR, wherein the amino acids at positions 482-517 are identical to SEQ ID NO :125 of the instant self-cleaving linker peptide.
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Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 52 of the anti-CD 19/anti-CD22 V8 CAR at amino acid positions 482-517 as taught by QIN et al. as the amino acid sequence of the linker in the CAR of QIN et al. represents nothing more than the substitution of one linker amino acid sequence for another with predictable results.
Regarding claim 27, Bitter et al. teaches a method of treating cancer in a subject (clams 1 and 21-23), wherein said method comprises administering, to said subject a population of T cells comprising a nucleotide sequence encoding a first polypeptide and a nucleotide sequence encoding a second polypeptide (column 13, lines 1-4, column 12, lines 14-20). Bitter et al. further teaches a composition comprising: (i) a first nucleic acid encoding, or a first polypeptide comprising a CAR molecule that binds CD19 and (ii) a second nucleic acid encoding, or a second polypeptide comprising a CAR molecule that binds a B-cell antigen, such as FLT-3 (Column 12, lines 20-26). Bitter et al. further teaches that the CD19 CAR comprises an scFv (column 28, lines 18-20), a CD28 hinge, a CD28 transmembrane domain (column 29, lines 55-62), CD28 intracellular signaling domain described herein and/or a CD3 zeta intracellular T cell signaling domain (column 17, lines 50-55). Bitter et al. further teaches that the FLT-3 CAR comprises an scFv, a CD8a hinge, a CD8a transmembrane domain (column 114, lines 7-19), 4-1BB intracellular signaling domain described herein and/or a CD3 zeta intracellular T cell signaling domain (column 21, lines 30-36). Bitter et al. also teaches that the nucleotide sequence encoding said first polypeptide is joined to said nucleotide sequence encoding said second polypeptide by a nucleotide sequence encoding a self-cleaving linker peptide (column 74, lines 20-24, column 145, lines 39-41, and column 75, lines 38-47).
However, Bitter et al. fails to teach that the self-cleaving linker peptide comprises the amino acid sequence set forth in instant SEQ ID NO: 125.
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However, QIN et al. teaches SEQ ID NO: 52 of the anti-CD 19/anti-CD22 V8 CAR, wherein the amino acids at positions 482-517 are identical to SEQ ID NO :125 of the instant self-cleaving linker peptide.
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 52 of the anti-CD 19/anti-CD22 V8 CAR at amino acid positions 482-517 as taught by QIN et al. as the amino acid sequence of the linker in the CAR of QIN et al. represents nothing more than the substitution of one linker amino acid sequence for another with predictable results.
Regarding claim 28: Following discussion of claim 27 above, Bitter et al. teaches that the cancer is acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) (column 14, lines 1-5).
Regarding claim 29: Following discussion of claim 28 above, Bitter et al. teaches that the ALL is B-cell ALL (B-ALL) (column 14, lines 1-5).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Hanan Isam Abuzeineh
/H.I.A./ Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633
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