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’s election without traverse of 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 is acknowledged.
Applicants have cancelled non-elected Groups II-IV, drawn to claims 23-26, 30-35, 39-40, and 36-38, respectively.
Applicants have also 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.
However, after further consideration, the election of species requirement of all the species groups is withdrawn. All species have been considered on the merits. Therefore, claims 1- 8, 10-22, and 27-29 are pending and under examination in the instant application.
Claim Interpretation
Claim 27 is understood to be directed to a host cell comprising the first and second polypeptides of either composition of claim 1 or composition of claim 2. This host cell is for use in the treatment of cancer in a subject.
The recitation “for use in the treatment of cancer in a subject” is an intended use, such that the claim doesn't require the use of the host cell, but only that it can be used. Therefore, claim is being interpreted as being drawn to any host cell that comprises the first and second polypeptides of either composition of claim 1 or composition of claim 2
and is configured for use in treatment of cancer.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 28-29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because “use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 28-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Regarding instant claims 28-29, they are “use” claims. The meets and bound of the claims are indefinite wherein the conjugate is claimed “for use”. MPEP 2173.05(q) states attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness. Recitation of a use without any active, positive steps delimiting how this use is actually practiced is indefinite.
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) 1-2, 5-8, 12-14, 19-22, and 27-29 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Bitter et al. (US10253086B2, filed on 04/08/2016, and published on 04/09/2019).
Regarding claim 1, Bitter et al. 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).
Regarding claim 2, Bitter et al. 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, a leader sequence, an scFv (column 28, lines 18-20), a CD8a hinge, a CD8a transmembrane domain (column 29, lines 55-62), 4-1BB 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, a leader sequence, 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 and column 118, lines 28-33).
Regarding claim 5: Following discussion of claim 1 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 110, which is at amino acid positions 246-284, identical to instant SEQ ID NO: 122 of the CD28 hinge region of the CD19 CAR.
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124
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Regarding claim 6: Following discussion of claim 1 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 110, which is at amino acid positions 285-311, identical to instant SEQ ID NO: 79 of the CD28 transmembrane domain of the CD19 CAR.
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123
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Regarding claim 7: Following discussion of claim 1 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 1317 of CD28 intracellular signaling domain, which is identical to instant SEQ ID NO: 123.
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120
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Regarding claim 8: Following discussion of claim 1 or 2 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 43 of CD3 zeta intracellular signaling domain, which is identical to instant SEQ ID NO: 124.
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179
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116
613
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Regarding claim 12: Following discussion of claim 1 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 14 of the CD8a hinge domain, which is identical to instant SEQ ID NO: 72.
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116
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Regarding claim 13: Following discussion of claim 1 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 15 of the CD8a transmembrane domain, which is identical to instant SEQ ID NO: 71.
Regarding claim 14: Following discussion of claim 1 or 2 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 16 of the 4-1BB intracellular signaling domain, which is identical to instant SEQ ID NO: 73.
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133
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Regarding claim 19: Following discussion of claim 1 or 2 above, Bitter et al. teaches an expression construct comprising a nucleotide sequence encoding the first polypeptide and the second polypeptide of the composition, wherein the nucleotide sequence encoding the first polypeptide is operably linked to a nucleotide sequence encoding the second polypeptide by a nucleic acid sequence that encodes a self-cleaving linker peptide (column 74, lines 20-24, column 145, lines 39-41, and column 75, lines 38-47).
Regarding claim 20: Following discussion of claim 1 or 2 above, Bitter et al. teaches a host cell comprising the first and second polypeptides of the composition (column 12, lines 55-61).
Regarding claim 21: Following discussion of claim 20 above, Bitter et al. teaches that the host cell is a T-cell (column 12, lines 55-61).
Regarding claim 22: Following discussion of claim 20 above, Bitter et al. teaches a population of cells comprising the host cell (column 13, lines 1-4).
Regarding claim 27: Following discussion of claim 20 above, Bitter et al. teaches that the host cell is used for treatment of cancer (column 13, lines 57-67).
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).
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) 1-4 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 Stephan et al. (US20160145348A1, filed on 03/14/2014, and published on 05/26/2016).
Regarding claims 1-2, the teachings of Bitter et al. are set forth in detail above.
Regarding claim 3: Following discussion of claim 1 or 2 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 58, which is at positions 22-128, 100% identical to instant SEQ ID NO: 34 and at positions 144-263, 100% identical to instant SEQ ID NO: 33 of the scFv of the CD19 CAR.
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184
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189
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However, Bitter et al. fails to teach that the amino acid sequence of the scFv of the CD19 CAR is 100% identical to instant SEQ ID NO: 67.
However, Stephan et al. teaches SEQ ID NO: 21 of the anti-CD19 scFv (VH-VL) FMC63 amino acid sequence, that is at amino acid positions 126-245 identical to instant SEQ ID NO: 33, at amino acid positions 108-125 identical to instant SEQ ID NO: 67, and at amino acid positions 1-107 identical to instant SEQ ID NO: 34.
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 21 of the anti-CD19 scFv (VH-VL) taught by Stephan et al. as the amino acid sequence of the anti-CD19 scFv of Bitter et al. as the use of the Stephan et al.’s sequence represents nothing more than the substitution of one scFv amino acid sequence for another with predictable results.
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Regarding claim 4: Following discussion of claim 1 or 2 above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 58, which is at positions 22-263, 95.1% similar to instant SEQ ID NO: 121 of the scFv of the CD19 CAR.
However, Bitter et al. fails to teach that the amino acid sequence of the scFv of the CD19 CAR is 100% identical to instant SEQ ID: 121.
However, Stephan et al. teaches SEQ ID NO: 21 of the anti-CD19 scFv (VH-VL) FMC63 amino acid sequence, which is identical to instant SEQ ID NO: 121.
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 21 of the anti-CD19 scFv (VH-VL) taught by Stephan et al. as the amino acid sequence of the anti-CD19 scFv of Bitter et al. as the use of the Stephan et al.’s sequence represents nothing more than the substitution of one scFv amino acid sequence for another with predictable results.
Claim(s) 1-2 and 10-11 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 Chien et al. (US12202902B2, effectively filed on 05/27/2016).
Regarding claims 1-2, the teachings of Bitter et al. are set forth in detail above.
Regarding claim 10: Following discussion of claim 1 or 2 above, Bitter et al. fails to teach the amino acid sequence of the scFv that binds FLT3.
However, Chien et al. teaches the amino acid sequence of SEQ ID NO: 29, which is at amino acids 1-244, identical to instant SEQ ID NO: 18 of the scFv that binds FLT3.
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 29 of the anti-FLT3 scFv taught by Chien et al. as the amino acid sequence of the anti- FLT3 scFv of Bitter et al. as the use of the Chien et al.’s sequence represents nothing more than the substitution of one scFv amino acid sequence for another with predictable results.
Regarding claim 11: Following discussion of claim 1 or 2 above, Bitter et al. fails to teach the amino acid sequence of the scFv that binds FLT3.
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However, Chien et al. teaches the amino acid sequence of SEQ ID NO: 29, which is at amino acids 1-246, identical to instant SEQ ID NO: 127 of the scFv that binds FLT3.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 29 of the anti-FLT3 scFv taught by Chien et al. as the amino acid sequence of the anti- FLT3 scFv of Bitter et al. as the use of the Chien et al.’s sequence represents nothing more than the substitution of one scFv amino acid sequence for another with predictable results.
Claim(s) 1-2 and 15-18 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 Stephan et al. (US20160145348A1, filed on 03/14/2014, and published on 05/26/2016) and Chien et al. (US12202902B2, effectively filed on 05/27/2016).
Regarding claims 1-2, the teachings of Bitter et al. are set forth in detail above.
Regarding claims 15 and 16: Following discussion of claims 1 and 2, respectively above, Bitter et al. teaches the amino acid sequence of SEQ ID NO: 58, which is at positions 22-263, 95.1% similar to instant SEQ ID NO: 121 of the scFv of the CD19 CAR, the amino acid sequence of SEQ ID NO: 110, which is at amino acid positions 246-284, identical to instant SEQ ID NO: 122 of the CD28 hinge region of the CD19 CAR (Please see the screenshot of the query match under the discussion of claim 5 above), the amino acid sequence of SEQ ID NO: 110, which is at amino acid positions 285-311, identical to instant SEQ ID NO: 79 of the CD28 transmembrane domain of the CD19 CAR (Please see the screenshot of the query match under the discussion of claim 6 above), the amino acid sequence of SEQ ID NO: 1317 of CD28 intracellular signaling domain, which is identical to instant SEQ ID NO: 123 (Please see the screenshot of the query match under the discussion of claim 7 above), the amino acid sequence of SEQ ID NO: 43 of CD3 zeta intracellular signaling domain of any of the CARs, which is identical to instant SEQ ID NO: 124 (Please see the screenshot of the query match under the discussion of claim 8 above), the amino acid sequence of SEQ ID NO: 14 of the CD8a hinge domain, which is identical to instant SEQ ID NO: 72 (Please see the screenshot of the query match under the discussion of claim 12 above), the amino acid sequence of SEQ ID NO: 15 of the CD8a transmembrane domain, which is identical to instant SEQ ID NO: 71 (Please see the screenshot of the query match under the discussion of claim 13 above), the amino acid sequence of SEQ ID NO: 16 of the 4-1BB intracellular signaling domain, which is identical to instant SEQ ID NO: 73 (Please see the screenshot of the query match under the discussion of claim 14 above).
However, Bitter et al. fails to teach that the amino acid sequence of the scFv of the CD19 CAR is 100% identical to instant SEQ ID: 121.
However, Stephan et al. teaches SEQ ID NO: 21 of the anti-CD19 scFv (VH-VL) FMC63 amino acid sequence, which is identical to instant SEQ ID NO: 121. (Please see the screenshot of the query match under the discussion of claim 4 above).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 21 of the anti-CD19 scFv (VH-VL) taught by Stephan et al. as the amino acid sequence of the anti-CD19 scFv of Bitter et al. as the use of the Stephan et al.’s sequence represents nothing more than the substitution of one scFv amino acid sequence for another with predictable results.
Also, Bitter et al. fails to teach the amino acid sequence of the scFv that binds FLT3.
However, Chien et al. teaches the amino acid sequence of SEQ ID NO: 29, which is at amino acids 1-244, identical to instant SEQ ID NO: 18 of the scFv that binds FLT3 (Please see the screenshot of the query match under the discussion of claim 10 above).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of SEQ ID NO: 29 of the anti-FLT3 scFv taught by Chien et al. as the amino acid sequence of the anti- FLT3 scFv of Bitter et al. as the use of the Chien et al.’s sequence represents nothing more than the substitution of one scFv amino acid sequence for another with predictable results.
Regarding claim 17, Bitter et al. in view of Stephan et al. and Chien et al. fails to teach that the first polypeptide comprises the amino acid sequence of SEQ ID NO: 141 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 142.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have joined the amino acid sequence of SEQ ID NO: 21 of the anti-CD19 scFv of Stephan et al., amino acid positions 246-284 of SEQ ID NO: 110 of the CD28 hinge domain of Bitter et al., amino acid positions 285-311, SEQ ID NO: 110 of the CD28 transmembrane domain of Bitter et al., SEQ ID NO: 1317 of CD28 intracellular signaling domain of Bitter et al., SEQ ID NO: 43 of CD3 zeta intracellular signaling domain of Bitter et al., respectively to arrive at the amino acid sequence of SEQ ID NO: 141 of the first polypeptide with a reasonable expectation of success. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have joined amino acids 1-244 of SEQ ID NO: 29 of the anti-FLT3 scFv of Chien et al., amino acid sequence of SEQ ID NO: 14 of the CD8a hinge domain of Bitter et al., amino acid sequence SEQ ID NO: 115 of the CD8a transmembrane domain of Bitter et al., SEQ ID NO: 16 of 4-1BB intracellular signaling domain of Bitter et al., SEQ ID NO: 43 of CD3 zeta intracellular signaling domain of Bitter et al., respectively to arrive at the amino acid sequence of SEQ ID NO: 142 of the second polypeptide with a reasonable expectation of success.
Regarding claim 18, Bitter et al. in view of Stephan et al. and Chien et al. fails to teach that the first polypeptide comprises the amino acid sequence of SEQ ID NO: 151 and the second polypeptide comprises the amino acid sequence of SEQ ID NO: 152.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have joined the amino acid sequence of SEQ ID NO: 21 of the anti-CD19 scFv of Stephan et al., amino acid sequence SEQ ID NO: 14 of the CD8a hinge domain of Bitter et al., amino acid sequence SEQ ID NO: 15 of the CD8a transmembrane domain of Bitter et al., SEQ ID NO: 16 of 4-1BB intracellular signaling domain of Bitter et al., SEQ ID NO: 43 of CD3 zeta intracellular signaling domain of Bitter et al., respectively to arrive at the amino acid sequence of SEQ ID NO: 151 of the first polypeptide with a reasonable expectation of success. Also, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have joined amino acids 1-244 of SEQ ID NO: 29 of the anti-FLT3 scFv of Chien et al., amino acid sequence of SEQ ID NO: 14 of the CD8a hinge domain of Bitter et al., amino acid sequence SEQ ID NO: 115 of the CD8a transmembrane domain of Bitter et al., SEQ ID NO: 16 of 4-1BB intracellular signaling domain of Bitter et al., SEQ ID NO: 43 of CD3 zeta intracellular signaling domain of Bitter et al., respectively to arrive at the amino acid sequence of SEQ ID NO: 152 of the second polypeptide with a reasonable expectation of success.
Conclusion
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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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633