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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, the certified copies are not English translations of CN201911301518.8 and CN202011274810.8.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C.119(a)-(d) prior to declaration of an interference, a certified English translation of theforeign application must be submitted in reply to this action. 37 CFR 41.154(b) and41.202(e).
Failure to provide a certified translation may result in no benefit being accordedfor the non-English application. The effective priority date is the filing date ofPCT/CN2020/136241 filed on 12/14/2020 in the absence of a certified translations of CN201911301518.8 and CN202011274810.8 filed on 12/17/2019 and 11/16/2020, respectively.
Election/Restrictions
Applicant’s election with traverse of Group II, claims 19-26 and 40-45 drawn to a method for treating a disease or disorder associated with CD19 expression by administering the CAR protein, nucleic acid molecule encoding the CAR, a vector comprising the nucleic acid molecule, or an immune effector cell comprising the protein, nucleic acid, or vector to a patient on 30 December 2025 is acknowledged. The traversal is on the ground(s) the Office has not met the burden to show a search and examination burden between the inventions (Remarks 12/30/2025 p. 1-2, at least in part because “the Office acknowledges that Groups I and II are related as product and process of use, the search and examination of Groups I and II would overlap with each other, and similar search parameters and terms could be used to search the prior art for both groups” (Remarks p. 2). This is not persuasive because as described in the Restriction/election requirement dated 11/05/2025, the inventions are independent and distinct and there is a serious search and/or examination because, among other reasons, the inventions have acquired a separate status in the art in view of their different classification. Applicants argue that searching and examining of Groups I and II would overlap with each other and similar search parameters and terms could be used for prior art for both groups. This is not persuasive because although the product and process of using do have overlap, they have acquired a separate status in the art in view of their different CPC classifications and would require different fields of search because prior art that applies to the product does automatically apply to the method of using, which must be searched separately. Further, there is an additional examination burden because of examination of the claims for compliance with the other statutes would not necessarily apply to the examination of the other claims. For example, the methods claims may encounter 112(a) enablement issues that require a further examination that do not apply to the invention of the composition. Therefore, the invention and independent and distinct, and there would be a serious search and examination burden for the Examiner to search and examine all of the groups.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-10 and 35-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/30/2025.
Applicant further elects the species of CD19-expressing disease of acute lymphoblastic leukemia. Claims 19-24 and 40-42 read on the elected species.
Claims 25-26 and 43-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. The species election is considered to be made without traverse in the reply filed on 12/30/2025 because the election did not specify with or without traverse but did not particularly point out any errors in the restriction, and therefore is treated as an election without traverse (MPEP §818.01(a)).
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 described in the Election/Restriction section above. Claims 19-24 and 40-42 are under consideration in the instant Office Action.
Claim Objections
Claim 19 is objected to because of the following informalities: Claim 19 refers to the chimeric antigen receptor according to claim 1, recites "the amino acid sequence as shown in SEQ ID NO. 1." First, "SEQ ID NO. 1" contains an internal period See MPEP 608.01(m). Second, “the amino acid sequence as shown in” is informal because the phrase “as shown” is not an art-recognized phrase to refer to the entirety of SEQ ID NO: 1. Appropriate correction is required. The examiner suggests amending the claim to recite “the amino acid sequence of SEQ ID NO:[[.]] 1.”
Claims 19, and 41-42 are objected to because they appear to inadvertently recite “administrating” and “administrated” rather than “administering” and “administered”. Appropriate correction is required.
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 24 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 24 is indefinite for the recitation of “wherein the step of administrating is administered at a dose of 0.25 x 108 to 0.5 x 108 CAR-positive T cells”. It is unclear how a step of administrating can be administered or whether the claim requires the CAR-positive T cells to be administered, or whether it may be “at a dose” of CAR-positive cells. For the purposes of expedited prosecution, the examiner will interpret claim 24 as reading “The method according to claim 23, wherein the step of administering comprises administering a dose of 0.25 x 108 to 0.5 x 108 CAR-positive T cells”. See also the objection above regarding “administrating” and “administering”.
Claim Rejections - 35 USC § 112(a)- Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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, because the specification, while being enabling for a) a method for treating a cancer expressing CD19 comprising administering one of: b) a nucleic acid encoding the chimeric antigen receptor according to claim 1, a vector comprising the nucleic acid molecule encoding the chimeric antigen receptor, or a T cell or NK cell comprising the chimeric antigen receptor of claim 1, the nucleic acid molecule encoding the CAR of claim, and the vector comprising the nucleic acid molecule encoding the CAR according to claim 1,
does not reasonably provide enablement for
a) a method of treating any generic disease or disorder associated with CD19 expression comprising administering one of the following, wherein the following includes b) administering the CAR polypeptide as recited in claim 19 or any immune effector cell comprising the CAR peptide, nucleotide sequence, or vector. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. In In re Wands, 8 USPQ2d 1400 (Fed. Cir., 1988) eight factors included for determining enablement:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The following is an analysis of these factors in relationship to this application.
Scope of the claims and nature of the invention
Claim 19 is directed towards a method of treating a generic disease or disorder “associated with CD19 expression” comprising the step of administering one or more of the following to a patient in need thereof: the chimeric antigen receptor according to claim 1, a nucleic acid molecule encoding the chimeric antigen receptor according to claim 1, a vector comprising the nucleic acid molecule encoding the chimeric antigen receptor according to claim 1, and an immune effector cell comprising one or more of the following: the chimeric antigen receptor according to claim 1, the nucleic acid molecule encoding the chimeric antigen receptor according to claim 1, and the vector comprising the nucleic acid molecule encoding the chimeric antigen receptor according to claim 1. Claim 1 is directed towards a chimeric antigen receptor comprising the amino acid sequence shown in SEQ ID NO: 1.
Claims 20-23 and 40 narrow the scope of the disease to non-solid tumors, leukemia and/or lymphoma, and acute lymphoblastic leukemia and/or B-cell lymphoma, but do not address the scope of administering a CAR peptide to treat disease.
Claims 41-42 narrow the methods to a single dose or administration by intravenous injection, respectively, but do not address the scope of enablement issues of claim 19.
State of the Relevant Art; level of ordinary skill; and level of predictability in the art
Methods of treating CD19-expressing cancers comprising administering an anti-CD19 CAR T and NK cells are known in the art. For example, NCT03373071 “Anti-CD19 CAR T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and NHL” published 23 December 2017 teaches a phase I study to evaluate safety and establish recommended dose of CD19-CART01 infused in pediatric patients affected by relapsed/refractory B-ALL or NHL with measurable bone marrow involvement (See Brief Summary). Ying, Zhitao, et al. "A safe and potent anti-CD19 CAR T cell therapy." Nature medicine 25.6 (2019): 947-953 teaches a different clinical trial of anti-CD19 CAR-T cell therapy in adults comprising administering 2 × 108–4 × 108 CD19-BBz(86) CAR T cells to treat B-cell lymphoma. Herrera, L., et al. "Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells." Scientific reports 9.1 (2019): 18729 teaches production of anti-CD19 CAR NK cells from peripheral blood and cord blood are cytotoxic against different cancer cell line target cells (Fig. 5).
Regarding administering a nucleic acid or a vector comprising a nucleic acid encoding the CAR, Agarwal, Shiwani, et al. "In vivo generated human CAR T cells eradicate tumor cells." Oncoimmunology 8.12 (2019): e1671761 teaches administration of a lentiviral vector encoding a CD19-CAR targeting CD8+ immune cells. The CAR was sufficient to eliminate CD19+ Nalm-6 cancer tumors cells when administered to mice with activated human PBMC (Fig. 1). However, there is no evidence of record of administering only a CAR peptide in order to treat a CD19-associated disease. There is no evidence that administration of the CAR could have an effect in the absence of its expression by an effector cell.
Regarding CD19-associated, there is no evidence of treatment in any generic disease associated with CD19 expression. In fact, the broadest reasonable interpretation of the claim with the phrase “a disease or disorder associated with CD19 expression” is that it could encompass a disease or disorder that has loss of CD19 expression because it is “associated with CD19 expression”. It is art-known that the effectiveness of an anti-CD19 CAR in treating cancer is dependent on the tumor cells expressing CD19. Sotillo, Elena, et al. "Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy." Cancer discovery 5.12 (2015): 1282-1295 teaches alternate splicing of CD19 in a mechanism of resistance to anti-CD19 CAR-T cells (Abstract, Fig. 5). There are no methods of treating a disease or disorder that is not a CD19-expressing cancer of record.
Summary of Species disclosed in the original specification; the amount of direction provided by the inventor, existence of working examples; and quantity of experimentation needed to make or use the invention based on the content of the disclosure
The instant specification discloses a CAR encoded by SEQ ID NO: 1, which is transduced into T cells via lentiviral transduction (Example 2). The CAR-T cells are tested for cytotoxicity in a variety of assays in vitro (Examples 4-6) and show cytotoxicity against CD19-expressing tumor cell lines. Example 11 demonstrates that for 3 different doses of CD19-CAR-T cells, the CAR-T extended the lifespan of mice with Nalm6 tumor xenografts compared to controls with the CAR-T cell therapy (Fig. 8). Additionally, the specification teaches a clinical trial of CAR-T cells (“CNCT19 cells”) in adults and children with relapsed or refractory acute lymphoblastic leukemia (ALL) (Example 12 p. 27-28, Table 2) and relapsed or refractory non-Hodgkin’s lymphoma (Example 12 p. 29-32, Table 7). There are no examples of administering the CAR peptide in order to treat a disease or disorder associated with the expression of CD19. There are no examples of administering to a subject with a disease or disorder associated with CD19 other than a cancer that expresses CD19.
Conclusion
The Applicant does not have enablement for the method of treating any generic disease or disorder associated with the expression of CD19 or for administering an isolated peptide encoding the CAR in a method of treating. It would take undue experimentation for a person of ordinary skill in the art to determine which diseases or disorders associated with CD19 expression can be treated, or to determine whether all of the methods of administering the peptide for a method of treating absent a T or NK cell comprising the peptide in order to act as an effector. Claims 20-23 and 40-42 are rejected for depending on claim 19 without sufficiently narrowing the scope.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 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.
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).
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.
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.
The teachings of NCT04011293 in regards 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 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. 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 41-BB 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, 41-BB, 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 in view of CN108949695 to Chen et. al. published 7 December 2018; CN10478857 to An et. al. published 22 July 2015; and WO2021068108 to Zeng et. al. effectively filed 8 October 2019. 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.
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.
Double Patenting- Non-Statutory 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 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.
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 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.
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.
The teachings of claims 1-14 of U.S. Patent No. 12441779 in regards 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.
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.
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/KATHLEEN CUNNINGCHEN/ Examiner, Art Unit 1646
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678