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 .
Response to Amendment
The Amendment filed 27 April 2026 is acknowledged. Applicant has amended claims 1, 19-20, 22, 24, and 41-42.
Claim Status
Claims 1-10, 19-26, and 35-45 are pending. Claims 1-10, 25-26, 35-39, and 43-45 are withdrawn from consideration as previously described. Claims 19-24 and 40-42 are under consideration in the instant Office Action.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Applicant has filed certified translations of the foreign priority document Chinese Patent Application No. 201911301518.8 filed on 17 December 2019 and Chinese Patent Application 202011274810.8 filed 16 November 2020. Accordingly, the instant claims are examined with an effective filing date of the foreign priority document, 17 December 2019.
Withdrawal of Objections
The objection to claims 19, and 41-42 are withdrawn in view of the amendment to the claims.
Withdrawal of Rejections
The rejection of claim 24 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second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn in view of the amendment to the claims.
The rejection of claims 19-23 and 40-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph for scope of enablement, is withdrawn in view of the amendment to the claims.
Claim Objections- New
Claims 19, 20, 22 are objected to because of the following informalities: claim 19 recites "A method for treating a disease or disorder expressing CD19" and claims 20 and 22 recite "wherein the disease or disorder expressing CD19". This is informal because it is ambiguous how a disease or disorder expresses a protein. The Examiner suggests amending the claim to recite "A method for treating a disease or disorder of a cell expressing CD19". Appropriate correction is required.
Claim Rejections - 35 USC § 102- Maintained
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.
Claims 19-23 and 40-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCT04011293 “A Clinical Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Injection (CNCT19) in the Treatment of Cluster of Differentiation 19 (CD19) Positive Relapsed or Refractory B Cell Malignancies”, Shadong University, published 8 July 2019 (PTO-892 1/27/2026).
NCT04011293 teaches a clinical study of anti-CD19 chimeric antigen receptor T-cell injection in the treatment of CD19 positive relapsed or refractory B cell malignancies comprising administering the CAR-T to adult (age 18 or older) with relapsed or refractory B-cell acute lymphoblastic leukemia patients a cell comprising administering a single dose of the CNCT19 CD19 CAR T cells via intravenous infusion (See Criteria, Arms and Interventions). Although NCT04011293 does not teach that CNCT19 CAR-T cells comprise a CAR of SEQ ID NO: 1, as evidenced by the instant specification, CNCT19 is the CAR of SEQ ID NO: 1 (Specification p. 14 line 33-p. 15 line 2).
Response to Arguments
Applicant’s arguments field 4/27/2026 have been fully considered but are not persuasive. Applicant argues that “The Office admits that NCT0411293 fails to disclose SEQ ID NO: 1, as required by claim 19, instead turning to Applicant's specification in an attempt to link CNCT19 described in NCT0411293 to SEQ ID NO: 1 in Applicant's specification, alleging that CNCT19 must comprise SEQ ID NO: 1. Id. A §102 rejection requires all claim elements to be present in a single reference and extrinsic evidence may "explain but not expand" the reference; thus, NCT04011293's failure to disclose a CAR consisting of SEQ ID NO:1 means that it cannot anticipate the instant claims. See MPEP §2131” (Rermaks 4/27/2026 p. 9). This is not persuasive for the following reasons:
MPEP §2131.01 states that an extra reference can be used to show an inherent characteristic of the thing taught by the primary reference. As described in the 102 rejection above, CNCT19 cells CAR-T cells are, inherently, the cells comprising an amino acid sequence of SEQ ID NO: 1. Further, MPEP §2121.I and §2121.02.I teach that the reference is presumed to be operable and that if one of ordinary skill in the art was not able to make the CNCT19 cells at the time of filing because SEQ ID NO: 1 was not publicly available “[…] applicant must provide evidence showing that a process for making was not known at the relevant time. See the following subsection for the evidentiary standard to be applied” (emphasis is the Examiner’s). Applicant’s arguments may not take the place of evidence. Further, MPEP §2112.V. states “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning tending to show inherency, the burden shifts to applicant to show an unobvious difference”. The Examiner suggests that the rejection may be overcome by 1) Providing evidence on the record, such as by a declaration, that SEQ ID NO: 1 was not publicly available as of the effective filing date, and therefore that the disclosure of NCT’293 was not enabled or 2) invoking the exception under 102(b)(1)(A) or 102(b)(1)(B), as the publication date of the reference is now within 1 year of the perfected priority date, or both.
Claim Rejections - 35 USC § 103- Maintained
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.
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.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over NCT04011293 “A Clinical Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Injection (CNCT19) in the Treatment of Cluster of Differentiation 19 (CD19) Positive Relapsed or Refractory B Cell Malignancies”, Shadong University, published 8 July 2019 (PTO-892 1/27/2026).
The teachings of NCT04011293 in regard to claims 19 and 23 are above. NCT04011293 does not explicitly teach the method according to claim 23, wherein the step of administering comprises administering a dose of 0.25 x 108 to 2 x 108 CAR-positive cells.
NCT04011293 teaches administering the CNCT19 CAR-T cells at a dose of 0.5 to 4 x 106 autologous CNCT19 transduced cells per kg body weight, with a maximum dose of 4 x 108 CNCT19 transduced cells. For adults weighing anywhere between 45 and 100 kgs, this is equivalent to a dose of .23 x 108 to and 4 x 108.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to treat adult patients with doses between 0.5 and 4 x 106 CAR-positive cells per kg body weight, resulting in patients between 45 and 100kgs receiving a fixed dose between .23 x 108 to and 4 x 108 total CAR-positive cells. It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to optimize the dose for safety and efficacy within the prior-art taught range that encompasses the entire instant range. This would have a predictable effect because an artisan would be able to optimize the drug for a safe and effective dose for each patient based on the particular features of that patient’s case. See MPEP §2144.05.
Claims--- 19-23 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020172177 to Sadelain et. al. effectively filed 18 February 2019 (PTO-892 1/27/2026) in view of CN108949695 to Chen et. al. published 7 December 2018 (Of record, cited on IDS dated 11/17/2022); CN104788573 to An et. al. published 22 July 2015 (Of record, cited on IDS dated 11/17/2022); and WO2021068108 to Zeng et. al. effectively filed 8 October 2019 (PTO-892 1/27/2026). Citations for the patents not in English refers to the Google machine translation.
Sadelain et. al. teaches a method of treating a CD19-expressing cancer comprising administering a T cell comprising an anti-CD19 CAR (p. 5 lines 19-24; p. 112 lines 9-p. 117 line3). Sadelain et. al. teaches anti-CD19 CAR T treatment of cancer and administration of the CAR-T to a mouse xenograft model, NALM6 leukemia (Example 1) (reads on claims 19, 20, 21). Regarding claim 22, Sadelain et. al. teaches the method for treating acute lymphoblastic leukemia (p. 136 lines 23-p. 137 line 2; p. 6 lines 4-15; p. 115 lines 5-9). Regarding claim 23, Sadelain et. al. teaches the treatment of human subjects (p. 25 lines 26-28) that are inherently either adults or children. Sadelain et. al. teaches embodiments of the CAR comprising a hinge/spacer region derived from a CD8a polypeptide, an intracellular signaling domain comprising a native CD3z polypeptide, and a co-stimulatory region of a 4-1BB polypeptide of SEQ ID NO: 118, wherein SEQ ID NO: 118 is 96.6% identical to the instant SEQ ID NO: 1:
RESULT 1
AASEQ2_01212026_210955
Query Match 96.6%; Score 2532; DB 1; Length 491;
Best Local Similarity 97.2%;
Matches 482; Conservative 3; Mismatches 3; Indels 8; Gaps 3;
Qy 1 MALPVTALLLPLALLLHAARPGSDIVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQ 60
|||||||||||||||||| || ||||||||||||||||||||||||||||||||||
Db 1 MALPVTALLLPLALLLHA-----DIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQ 55
Qy 61 QKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 56 QKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYT 115
Qy 121 SGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWM 180
||||||||||||||||||||||||||:|:|||||||||||||||||||||||||||||||
Db 116 SGGGTKLEIKRGGGGSGGGGSGGGGSEVKLQQSGAELVRPGSSVKISCKASGYAFSSYWM 175
Qy 181 NWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176 NWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVY 235
Qy 241 FCARKTISSVVDFYFDYWGQGTTLTVSSEF--TTTPAPRPPTPAPTIASQPLSLRPEACR 298
|||||||||||||||||||||||:|||| ||||||||||||||||||||||||||||
Db 236 FCARKTISSVVDFYFDYWGQGTTVTVSSAAAPTTTPAPRPPTPAPTIASQPLSLRPEACR 295
Qy 299 PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYC-KRGRKKLLYIFKQPFMRP 357
||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||
Db 296 PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNKRGRKKLLYIFKQPFMRP 355
Qy 358 VQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLD 417
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 356 VQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLD 415
Qy 418 KRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTA 477
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 416 KRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTA 475
Qy 478 TKDTYDALHMQALPPR 493
||||||||||||||||
Db 476 TKDTYDALHMQALPPR 491
And wherein the scFv of the CAR is 98.4% identical to the instant scFv:
DOCUMENT TYPE: Patent
PATENT INFORMATION: WO 2020172177 ***20200827***
PRIORITY INFO.: US 2019-62807181 20190218
FILE SEGMENT: PROTEIN; PS
MOLECULE TYPE: protein
PAT. SEQ. LOC: SEQ ID NO 118
ALIGN
ALIGNMENT FROM L-NUMBER L15
Query Length: 245; Sequence Length: 491;
Score: 447.2 bits (1149), 99.2% of highest possible score 450.7;
Expect value: 3.562e-124;
Identities: 241 / 245 (98.4%); Positives: 244 / 245 (99.6%);
Query Identity: 98.4%; Query Coverage: 100.0%;
Subject Identity: 49.1%; Subject Coverage: 49.9%;
Alignment Length: 245;
Q: 1 DIVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGVPD 60
|| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 19 DIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGVPD 78
Q: 61 RFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGGGTKLEIKRggggsggggsgg 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 79 RFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGGGTKLEIKRGGGGSGGGGSGG 138
Q: 121 ggsqvqlqqsgAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGD 180
|||+|+||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 139 GGSEVKLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGD 198
Q: 181 TNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTISSVVDFYFDYWGQGTT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 199 TNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTISSVVDFYFDYWGQGTT 258
Q: 241 LTVSS 245
+||||
S: 259 VTVSS 263
Sadelain et. al. does not teach exactly an scFv comprising the VH and VL of instant SEQ ID NO: 1.
This is resolved by Chen et. al. and An et. al.
Chen et. al. teaches a CAR of SEQ ID NO: 2 “CMV-CSF2RA-CD19 single chain antibody (scFv)-CD8 alpha-CD28-4-1BB-CD3 zeta-T2A-IL18 CAR construct (RZ-FMC63-28bbZ-IL18) sequence 91.4% identical to the instant SEQ ID NO: 1 and with identical CDRs to that of Sadelain et. al.:
Query Match 91.4%; Score 2397; Length 746;
Best Local Similarity 86.0%;
Matches 462; Conservative 9; Mismatches 20; Indels 46; Gaps 3;
Qy 1 MALPVTALLLPLALLLHAARPGSDIVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQ 60
| | ||:|| | | | | |||||||||||||||||||||||||||||||||||||||
Db 1 MLLLVTSLL--LCELPHPAFLGSDIVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQ 58
Qy 61 QKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 59 QKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYT 118
Qy 121 SGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWM 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 119 SGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWM 178
Qy 181 NWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 179 NWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVY 238
Qy 241 FCARKTISSVVDFYFDYWGQGTTLTVSSEFTTTPAPRPPTPAPTIASQPLSLRPEACRPA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 239 FCARKTISSVVDFYFDYWGQGTTLTVSSEFTTTPAPRPPTPAPTIASQPLSLRPEACRPA 298
Qy 301 AGGAVHTRGLDFACDIYIWAPLAG--TCGVLLLSLVITLY-------------------- 338
||||||||||||||| :: : | | ||::: ::
Db 299 AGGAVHTRGLDFACDFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPR 358
Qy 339 ----------------------CKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEE 376
|||||||||||||||||||||||||||||||||||||
Db 359 RPGPTRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEE 418
Qy 377 GGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQ 436
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 419 GGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQ 478
Qy 437 EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 493
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 479 EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 535
Chen et. al. teaches the preparation of a T-cell comprising the CAR and IL-18 for the treatment of CD19 expressing tumor cells (Embodiment 3). Chen et. al. therefore teaches that the scFv of the CAR 1) binds and functions as a CAR.
An et. al. teaches a CAR of SEQ ID NO: 1 which is 86.5% identical to the instant SEQ ID NO: 1, and has 100% identity to the scFv, hinge, transmembrane, and CD3z regions:
Qy 1 MALPVTALLLPLALLLHAARPGSDIVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MALPVTALLLPLALLLHAARPGSDIVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQ 60
Qy 61 QKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 QKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYT 120
Qy 121 SGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWM 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAELVRPGSSVKISCKASGYAFSSYWM 180
Qy 181 NWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVY 240
Qy 241 FCARKTISSVVDFYFDYWGQGTTLTVSSEFTTTPAPRPPTPAPTIASQPLSLRPEACRPA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 FCARKTISSVVDFYFDYWGQGTTLTVSSEFTTTPAPRPPTPAPTIASQPLSLRPEACRPA 300
Qy 301 AGGAVHTRGLDFACDIYIWAPLAG--TCGVLLLSLVITLYCKRGRKKLL----YIFKQPF 354
||||||||||||||| :: : | | ||::: :: | :: | |: |
Db 301 AGGAVHTRGLDFACDFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTP- 359
Qy 355 MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD 414
|| | : : | : |||||||||||||||||||||||||||||||||
Db 360 RRPGPTRKHYQPYA---PPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD 416
Qy 415 VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGL 474
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 417 VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGL 476
Qy 475 STATKDTYDALHMQALPPR 493
|||||||||||||||||||
Db 477 STATKDTYDALHMQALPPR 495
An et. al. teaches that the scFv comprises the light and heavy chain of the anti-human CD19 monoclonal antibody HI19a. An et. al. teaches that the scFv is codon-optimized. An et. al. teaches that the CAR of SEQ ID NO: 1 is cytotoxic when co-cultured with CD19 positive Nalm-6 cells in vitro (Fig. 8) and that it is expressed on the surface of T cells (Fig. 5). The only difference between instant SEQ ID NO: 1 and SEQ ID NO: 1 of An et. al. is that An et. al. uses a CD28 co-stimulatory domain rather than a 4-1BB co-stimulatory domain.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute the scFv sequences of Chen et. al. and the signal peptide-scFv of An et. al. in order to benefit from an optimized anti-CD19 CAR sequences effective for killing CD19 T cells because Chen et. al. and An et. al. teaches that scFv is effective for binding and killing CD19 expressing tumor cells. This would have a predictable effect because the CARs of Sadelain et. al., Chen et. al., and An et. al. are anti-CD19 CARs with the same CDRs, and therefore an artisan would expect that since both are effective for inducing T-cell cytotoxicity against CD19-expressing tumor cells that the equivalent portions may be substituted.
Sadelain et. al., Chen et. al., and An et. al. do not teach the transmembrane domain and intracellular portion of the CAR comprising the amino acid sequence identical to residues 269-493 of instant SEQ ID NO: 1.
This deficiency is resolved by Zeng et. al. Zeng et. al. teaches and anti-NKG2D CAR comprising a transmembrane domain and an intracellular signaling domain of SEQ ID NO: 1 residues 126-350 which is 100% identical to instant SEQ ID NO: 1 residues 269-493 comprising the hinge and transmembrane domain and the intracellular signaling domain. Zeng et. al. teaches that the intracellular signaling domain of the CAR of SEQ ID NO: 1 is effective at activating cytotoxicity in T cells in response to antigen binding against different tumor cell lines (See Fig. 4).
RESULT 1
US-18-056-616-1
Query Match 63.9%; Score 1223; DB 1; Length 493;
Best Local Similarity 67.4%;
Matches 246; Conservative 15; Mismatches 40; Indels 64; Gaps 7;
Qy 13 ICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTN 72
| | : | | || : : : |:| :: | :
Db 166 ISCKASGYAFSSYWMNWVKQRPG-----------------------QGLEWIGQIY-PGD 201
Qy 73 GSWQWEDGSILSPNLLTIIEMQKGDCALYA--SSFKGYIE----NCSTPNTYICMQRTV- 125
| : :| || | | || |:: | | ::|:
Db 202 GDTNY-NGKF------------KGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTIS 248
Qy 126 --------------------EFTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR 165
||||||||||||||||||||||||||||||||||||||||
Db 249 SVVDFYFDYWGQGTTLTVSSEFTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR 308
Qy 166 GLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCS 225
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 309 GLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCS 368
Qy 226 CRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG 285
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 369 CRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG 428
Qy 286 KPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ 345
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 429 KPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ 488
Qy 346 ALPPR 350
|||||
Db 489 ALPPR 493
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute the hinge, transmembrane, and intracellular signaling domain sequence of SEQ ID NO: 1 of Zeng et. al. for the hinge, transmembrane, and intracellular signaling domain sequences of Sadelain et. al. in view of Chen et. al. and An et. al. in order to benefit from the effective activation of T cell signaling in response to antigen binding as taught by Zeng et. al. This would have a predictable effect because Sadelain et. al. teaches alternative hinge and An et. al. teaches the exact scFv-hinge-transmembrane domain sequences, Sadelain et. al. teaches the 4-1BB costimulatory domain and CD3 zeta sequences with high sequence identity to those of Zeng, and therefore an artisan would expect to be able to substitute two suitably equivalent CAR-T backbones and make an effective CAR for activating T cells and would understand from the teachings of Sadelain et. al. that the particular CD8a hinge and transmembrane, 4-1BB, and CD3z sequences of Zeng et. al. fall under the scope of those described by Sadelain et. al.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute the leader peptide of Sadelain et. al. for the leader peptide of Wang et. al. in order to benefit from the effective and preferred driving of CAR surface expression by the CD8a leader sequence. This would have a predictable effect because an artisan Wang et. al. teach that there are many suitable leader peptides and therefore an artisan would expect to be able to exchange them.
To summarize, it would have been obvious for a person of ordinary skill in the art, before the effective filing date, to construct a CAR with the anti-CD19 scFv as taught by Chen et. al. and signal peptide/scFv as taught by An et. al., the CAR backbone (CD8a hinge and transmembrane, 4-1BB costimulatory domain, and CD3z intracellular domain) of Zeng et. al. in order to construct an alternate sequence of a CAR with art-known domains that are effective for T cell signaling upon CD19 antigen binding with: a signal peptide, the anti-CD19 scFv with identical CDRs, CD8a hinge and transmembrane domain, 4-1BB costimulatory domain, and CD3z domain as taught by Sadelain et. al. (See MPEP §2144.06). It would have been obvious to use the modified CAR is a method of treatment as taught by Sadelain as an equivalent CAR for the same use. This would have a predictable effect because Sadelain, Chen, An, and Zeng each teach that the respective sequence are equivalent domains that make a functional CAR (e.g. the human CD8a hinge of Sadelain and the human CD8a hinge of Zeng et. al. would be considered to be sequence variants of each other).
Claims 24 and 40-42 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020172177 to Sadelain et. al. effectively filed 18 February 2019 (PTO-892 1/27/2026) in view of CN108949695 to Chen et. al. published 7 December 2018 (PTO-892 1/27/2026); CN10478857 to An et. al. published 22 July 2015 (PTO-892 1/27/2026); and WO2021068108 to Zeng et. al. effectively filed 8 October 2019 (PTO-892 1/27/2026) as applied to claims 19 and 23 above, and further in view of NCT03373071 “Anti-CD19 CAR T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and NHL” by Bambino Gesu Hospital and Research Institute published 23 December 2017 (PTO-892 1/27/2026).
Modified Sadelain et. al. as described in the 103 rejection above does not teach wherein the disease or disorder is ALL, wherein the step of administering comprises a administering a dose of 0.25x108 to 0.5 x 108 CAR-positive T cells (claim 24), and wherein the ALL is relapsed or refractory ALL (claim 40), the CAR-positive cells are administered in a single dose (claim 41), and the CAR-positive T cells are administered by intravenous injection.
This deficiency is resolved by NCT03373071.
NCT03373071 teaches a method of treating pediatric CD19+ relapsed/refractory ALL by administering CAR-T cells expressing an anti-CD19 CAR in a single intravenous dose (Detailed description, Arms and Interventions).
NCT03373071 teaches that the dose is between 0.5 to 3.0 x 10⁶/kg (Arms and Interventions). For children 30-70 kg, this is a total dose from 0.15-2.1 x 108, which is a range that significantly overlaps with the instant range of 0.15-2.1 x 108.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to use the anti-CD19 CAR-T cells of modified Sadelain et. al. in the method of treating of NCT03373071 in order to benefit from an alternate effective cytotoxic CAR sequence as taught by Sadelain et. al. in a patient population that is expected to benefit from anti-CD19 CAR-T therapy as taught by NCT03373071.
Regarding claim 24, it would have been obvious for a person of ordinary skill in the art, before the effective filing date, to administer a CAR-T does of 0.15-2.1 x 108 and to optimize the dose for safety and efficacy within the prior-art taught range that encompasses the entire instant range. This would have a predictable effect because an artisan would be able to optimize the drug for a safe and effective dose for each patient based on the particular features of that patient’s case. See MPEP §2144.05.
Response to Arguments
Applicant’s arguments field 4/27/2026 have been fully considered but are not persuasive.
Regarding the rejection of claim 24 over NCT’293, Applicant argues that in the same manner as described for the §102 rejection, NCT’293 does not teach SEQ ID NO: 1. This response is unpersuasive for the reasons described in response to the 102 arguments above. Namely, a reference is presumed to be enabling and SEQ ID NO: 1 is an inherent feature of the disclosure of NCT’293; therefore, Applicant must provide evidence to show that the disclosure of NCT’293 was not enabled if SEQ ID NO: 1 was not publicly available.
Regarding the rejection of claims 19-23 over Sadelain in view of Chen, An, and Zheng Applicant argues that “As acknowledged by the Office, none of the references, alone or in combination, teach each and every element of the amended claims […] None of the references discloses are CAR consisting of SEQ ID NO: 1, and therefore the cited references do not teach or suggest all limitations of the amended claims”. This is not persuasive because, as described in the 103 rejection above, the combination of Sadelain in view of Chen, An, and Zheng makes obvious instant SEQ ID NO: 1 by each disclosing highly structurally sequences and art-equivalent domains in order to arrive at a CAR consisting of SEQ ID NO: 1. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant further argues that a person of ordinary skill in the art (POSA) would not have been motivated to combine the cited references to arrive at Applicant’s specific sequence-defined CAR because the Office relies on similarity of domains and does not supply a motivation to modify the amino acid sequence of each CAR element. Applicant states that “There is no teaching or suggestion in Sadelain that would motivate a POSA to deviate from any of the sequences disclosed therein” or to modify specific parts (Remarks p. 12). MPEP §2144.06 states that, in regard to art-recognized equivalents useful for the same purpose “An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)”. Therefore, as described in the 103 rejection above, it would have been obvious to substitute art-known equivalent sequences (e.g. the anti-CD19 scFv of Sadelain comprising the same CDRs and useful for the same purpose of binding CD19 in the context of a chimeric antigen receptor is obvious to substitute for the art-known anti-CD19 scFv or signal peptide-scFv with identical CDRs and nearly identical VH/VL domain of Chen and An). Applicant argues that the sequence similarity of the components to each other does not motivate substitution. This is not persuasive because a POSA would understand from the sequence similarity (e.g. 100% identity to the CDRs, greater than 95% identity to the VH/VL) that these domains would have highly similar functions and therefore be art-equivalent sequences to be used for the same purpose with a reasonable expectation of success.
Applicant argues that Chen et. al. teaches away from combining its disclosure with other CAR construct components and would have directed a POSA towards particular features such as a CD28 co-stimulatory domain and an IL-18 expression region (Remarks p. 13-15). First, MPEP §2141.02.VI. states that “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed”. As described by Applicant, Chen et. al. teaches that without IL-18 killed 50% of the target cells. This would be considered by a person of ordinary skill in the art to be a functional CAR. Further, the Examiner notes that the instant claims are directed towards a method of treating a disease or disorder expressing CD19 comprising administering “an immune effector cell comprising the chimeric antigen receptor, the nucleic acid molecule encoding the chimeric antigen receptor, and the vector comprising the nucleic acid molecule encoding the chimeric antigen receptor”; the examiner notes that both the vector and the nucleic acid molecule encoding comprise the chimeric antigen receptor, and the IL-18 is separated from the CAR of Chen by a T2A ribosomal skipping site; and therefore a POSA would not understand the CAR to consist of the additional IL-18, but rather to be a separate protein encoded in the vector, which is not excluded by the instant claims. Lastly, the disclosure of Chen is only used in the context of each of the other references to show that a POSA would understand that the scFv with 100% sequence identity to the instant CAR and the same CDRs of Sadelain is art-equivalent to the scFv of Sadelain because it binds to CD19 and induces T-cell activation in the context of a CAR; as shown by Sadelain, a POSA would understand that these art-equivalent scFvs would be expected to work on a backbone with either a 4-1BB domain as taught by Sadelain et. al. or a CD28 domain as taught by Chen et. al. In addition, the 50% kill percentage of the CAR alone group in Chen et. al. would serve as motivation for a POSA to make modifications to the CAR, such as to the co-stimulatory domain, to improve the activation and signaling in order to have higher T-cell killing. Therefore, Chen does not teach away from the instant SEQ ID NO: 1.
Applicant argues that An likewise teaches only CD28-based structures that would not have motivated one skilled in the art to arrive at the instant CAR because An would have directed a POSA to adopt the entire CAR architecture of An rather than replacing part of a domain. This is not persuasive, because a person of ordinary skill in the art at the time of filing had a basic understanding that the architecture of CARs could be altered by swapping domains with a reasonable expectation of making a functional CAR molecule (Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017 Jun 24;5:22). An teaches that the scFv is an art-equivalent anti-CD19 binder for use in a functional CAR molecule; therefore, it would have been obvious to a person of ordinary skill in the art that that scFv would be able to be exchanged for the art-equivalent scFv of Sadelain. Both Sadelain and An show that these are functional CARs that bind CD19 and activate; therefore, even above the general understanding in the art of the function of different co-stimulatory domains, a person of ordinary skill in the art would have understood that these two scFvs with highly similar structures and functions showed efficacy on two CAR backbones, one with a 4-1BB costimulatory domain and the other with a CD28 costimulatory domain. Thus, there was motivation to exchange the two scFvs as art-equivalent scFvs. The Applicant is reminded that the test for obviousness in not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). The combination of the claimed reference would, by a POSA, be expected to be functional for its purpose of binding CD19 and activating T-cells upon binding.
Applicant argues that even if Zeng discloses the backbone elements, the NKG2D binding domain of Zeng is fundamentally different context than the CD19 scFv of Sadelain, there is not motivation to replace the intracellular domain of Sadelain with that of Zeng. This is not persuasive. As described in the 103 rejection above, Sadelain teaches all of the elements of the CAR backbone of Zeng by naming the genus of domains (the CAR comprising a hinge/spacer region derived from a CD8a polypeptide, an intracellular signaling domain comprising a native CD3z polypeptide, and a co-stimulatory region of a 4-1BB polypeptide); the differences between Zeng and Sadelain are only 4 amino acids in the CD8-derived hinge region attaching the end of the scFv to the CAR backbone. There is a reasonable expectation of success in substituting the backbone of Zeng for the backbone sequence of Sadelain because a POSA would understand these backbones to be almost identically structurally similar and therefore would be art-known equivalents. A POSA would not expect that substituting different art-known CD8-derived hinges would critically change the function of a CAR such that it would no longer be useful for the intended purpose.
Applicant further argues that because there is no reasonable expectation of success because the entire structure of a chimeric antigen receptor is critical to its stability on the surface of immune cells, expression level, and cytotoxicity (Remarks p. 17-18). This is not persuasive because a POSA would have a reasonable expectation that the claimed characteristics would naturally flow from the obvious CAR sequence of modified Sadelain as described above. For instance, Sadelain teaches that the anti-CD19 4-1BB CAR of SEQ ID NO: 114 expresses approximately 60% of CAR-T cells across multiple experiments with an MFI of around 104. The instant CAR expresses in 68.6% of T cells in a single experiment at an MFI of slightly less than 104; there is a reasonable expectation of success the expression levels and stability that the art-known CAR of Sadelain substituted with art-equivalent CD19 and CAR backbone domains would result in expression levels and stability within the approximate range taught by Sadelain because the instant references teach that each of these domains is functional and stable within very highly similar contexts. Regarding cytotoxicity, the instant CAR prolong mouse survival at least 45 days in an in vivo mouse model at the highest dose of 2x107 (Specification Fig. 8); Sadelain et. al. shows a similar survival trajectory against an unmodified CD19-expressing NALM6 line from mice treating with 0.2x106 CAR-T cells (Fig. 2B). There is a reasonable expectation that a person of ordinary skill in the art can modify these sequences with art-known variations taught to be useful for the same purpose to arrive at a CAR with similar function to the closest prior art CAR of Sadelain.
Regarding the rejection of claims 24 and 40-42 in further view of NCT’071, Applicant argues that because NCT’071 is silent on the construct components and for the reasons above, it does not resolve the deficiencies of the other cited prior art. This is unpersuasive for the reasons described above.
Double Patenting- Non-Statutory Double Patenting- Maintained
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 19-24 and 40-42 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11547728 in view of NCT03373071 by Bambino Gesu Hospital and Research Institute published 23 December 2017 (PTO-892 1/27/2026).
The ‘728 patent teaches a chimeric antigen receptor consisting of the amino acid sequence of SEQ ID NO: 1 (claim 1), an immune effector cell comprising the chimeric antigen receptor according to claim 1 (claim 2) wherein the immune effector cell is selected from the group consisting of T lymphocytes and a natural killer cell (claim 3 and 7), a composition comprising the cells (claims 4 and 5), and wherein SEQ ID NO: 1 is expressed on the surface of the immune effector cell (claim 8).
The claims of ‘728 do not teach a method of treating a disease or disorder comprising administering the CAR-T cells or composition comprising the CAR-T cells expressing SEQ ID NO: 1.
This deficiency is resolved NCT03373071.
NCT03373071 teaches a method of treating pediatric CD19+ relapsed/refractory ALL by administering CAR-T cells expressing an anti-CD19 CAR in a single intravenous dose (Detailed description, Arms and Interventions).
NCT03373071 teaches that the dose is between 0.5 to 3.0 x 10⁶/kg (Arms and Interventions). For children 30-70 kg, this is a total dose from 0.15-2.1 x 108, which is a range that significantly overlaps with the instant range of 0.15-2.1 x 108.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to use the anti-CD19 CAR-T cells of ‘728 in the method of treating of NCT03373071 in order to benefit from an alternate effective cytotoxic CAR sequence in a patient population that is expected to benefit from anti-CD19 CAR-T therapy as taught by NCT03373071.
Regarding claim 24, it would have been obvious for a person of ordinary skill in the art, before the effective filing date, to administer a CAR-T dose of 0.15-2.1 x 108 and to optimize the dose for safety and efficacy within the prior-art taught range that encompasses the entire instant range. This would have a predictable effect because an artisan would be able to optimize the drug for a safe and effective dose for each patient based on the particular features of that patient’s case. See MPEP §2144.05.
Claims 19-24 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-14 of U.S. Patent No. 12441779 B1. Although the claims are not identical, they are not patentably distinct because the claims of ‘779 anticipate the instant claims.
The ‘779 patent teaches a method for treating a disease or disorder associated with CD19 expression comprising administering to a patient in need thereof a composition comprising a modified immune effector cell wherein the modified immune effector cell is prepared by a method of introducing a plasmid combination into a cell to prepare a lentiviral vector wherein the Seq1 plasmid comprises a nucleic acid molecule encoding a CAR comprising the amino acid sequence of SEQ ID NO: 1 (100% identical to instant SEQ ID NO: 1) and introducing the lentiviral vector into an immune effector cell (claim 1), wherein the disease or disorder associated with CD19 expression comprises non-solid tumors (claim 2); wherein the non-solid tumor comprises leukemia or lymphoma (claim 3); wherein the disease or disorder associated with CD19 expression is acute lymphoblastic leukemia (ALL) and/or B-cell lymphoma (claim 4); wherein the ALL comprises ALL in adults and/or in children (claim 5); wherein the composition is administered at a dose of 0.25 x 108 to 0.5 x 108 CAR-positive T cells (claim 6); wherein the composition is administered at a dose of 1x108 to 2x108 CAR-positive T cells (claim 8); wherein the ALL is relapsed or refractory ALL (claim 9). Although the claims are not identical, they teach all of the same limitations and therefore anticipate the instant method.
Claims 41-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12441779 B1 as applied to claims 19 and 23 above, in further view of NCT03373071 by Bambino Gesu Hospital and Research Institute published 23 December 2017 (PTO-892 1/27/2026).
The teachings of claims 1-14 of U.S. Patent No. 12441779 in regard to claims 19 and 23 are in the NSDP rejection above.
Claims 1-14 of the ‘779 patent do not explicitly teach that the method of treating relapsed/refractory ALL in a single dose administered by intravenous injection. This deficiency is resolved by NCT03373071.
NCT03373071 teaches a method of treating pediatric CD19+ relapsed/refractory ALL by administering CAR-T cells expressing an anti-CD19 CAR in a single intravenous dose (Detailed description, Arms and Interventions).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to use the anti-CD19 CAR-T cells of ‘779 in the method of treating of NCT03373071 in order to benefit from a particular method of administering and number of doses as taught by the prior art expected to be effective for a particular relapsed/refractory ALL population as taught by NCT03373071. This would have a predictable effect because an artisan would expect to be able to administer similar anti-CD19 CAR-T cells in a related method in a single dose and by the method as taught for an art-known population and method of treating.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive. Applicant argues that the rejection is overcome by the filed Terminal Disclaimers. However, as described in the Terminal Disclaimer review decision dated 5/20/2026, the filed terminal disclaimers have been disapproved. The terminal disclaimers were disapproved because the Terminal Disclaimer identified a party who is not the Applicant by inadvertently using the Applicant’s previous name “Juventas Cell Therapy LTD.” rather than the current Applicant name “Juventas Co., LTD”. The Examiner requests that new Terminal Disclaimers be filed with the Applicant name “Juventas Co., LTD”. As described in the attached Interview Summary, a phone call was placed to Applicant’s representative Li Feng on 5/28/2026 and Applicant’s representative stated that new terminal disclaimers would be filed in response to an Office Action.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Gu, Runxia, et al. "Phase 1 Results of CNCT19: CD19 CAR Constructed of a New Anti-CD19 Chimeric Antigen Receptor in Relapsed or Refractory Acute Lymphoblastic Leukemia." Blood 134 (2019): 2622 (PTO-892 1/27/2026).
THIS ACTION IS MADE FINAL. 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.
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/KATHLEEN CUNNINGCHEN/ Examiner, Art Unit 1646
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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