DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 4/25/25 in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/27/25 has been entered. Upon reconsideration, SEQ ID NO: 17-18 are being included in the examination.
Claims 1-4, 6, 10-19, 21-31 are pending.
Claims 26-31 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1-4, 6, 10-19, 21-25 are being acted upon.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 6, 10-19, 21-25 are 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 1 is indefinite in the recitation of a CAR comprising the “six CDRs” of the recited SEQ ID Nos. The scope of the actual residues encompassed by the instant claims is unclear and indefinite, since different numbering schemes exist for defining CDR residues, and the instant specification does not define the metes and bounds of the claimed CDRs. The instant specification discloses in paragraph 72 that CDR sequences can be determined by one of skill in the art as a routine matter, and states that available resources are known in the art, for example, see Wu J.Ex.Med 132: 211-250 (1970), IMGT, and Paratome web server. However, citing exemplary CDR numbering schemes is not sufficient definition of the claim scope. For example, would the claims encompass other CDR numbering schemes, such as Martin numbering? Would the claims encompass a combination of different numbering schemes, i.e. CDR1 as defined in IMGT, CDR2 as defined by Paratome? The scope of the clams cannot be established.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 1-3, 6, 10-19, 21-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0362472, in view of WO 2015/187528 and US 20070014720 (all of record).
The ‘472 publication teaches a nucleic acid encoding i) first CAR that binds to CD19, and ii) a second CAR that binds to CD20, wherein a nucleic acid sequence encoding a protease cleavage site, such as F2A, is situated between the nucleic acid sequences encoding i) and ii) such that a cell can express a fusion protein comprising i) and ii), which protein is subsequently separated into two polypeptides by proteolytic cleavage (i.e. one or more polypeptides encoded by said nucleic acid, see paragraph 63, in particular). The ‘472 publication teaches said nucleic acid in a vector, and an immune effector cell comprising said vector, wherein the cells express the encoded proteins (See page 7, in particular). The ‘472 publication teaches a pharmaceutical composition of said immune effector cells (see pages 8-9 and paragraph 118, in particular). The ‘472 publication teaches that the CD19 CAR comprises an anti-CD19 scFV, a hinge and transmembrane domain, and an intracellular signaling domain (See pages 14-16, in particular). The ‘472 publication teaches that said scFV is in the form of leader sequence, light chain variable region-linker-heavy chain variable region (see page 16, in particular). The ‘472 publication teaches a leader sequence of SEQ ID NO: 13, which is identical to SEQ ID NO:3 of the instant application. The ‘472 publication teaches a hinge/transmembrane domain of CD8. The ‘472 publication teaches that the intracellular signaling domain comprises CD28 or 4-1BB costimulatory domain and a CD3 zeta sequence (see pages 14-16 and Fig 1, in particular). For example, the ‘472 application teaches that when the first CAR is a CD19 CAR, and the second CAR is a CD20 CAR, the first and second CAR can comprise the same or different intracellular signaling domains (See page 10, in particular). The ‘472 publication teaches that in some embodiments the CD19 CAR can comprise a CD3zeta signaling domain and a CD28 costimulatory domain, and the CD20 CAR comprises the same intracellular signaling domain (See page 10, in particular). Alternatively the ‘472 publication also teaches that in some embodiments, the CD19 CAR and CD20 CAR both comprise a CD3zeta signaling domain, but can comprise different costimulatory domains, i.e. the CD19 CAR comprises a CD28 signaling domain and the CD20 CAR comprise a 41BB signaling domain (See page 10, in particular). The ‘472 publication teaches a CD3 zeta of SEQ ID NO: 17, which is identical to Seq ID NO: 9 of the instant application, and a 4-1BB sequence of SEQ ID NO: 16, which is identical to SEQ ID NO: 14 of the instant application. The ‘472 publication teaches a CD28 sequence identical to SEQ ID NO: 8 of the instant application (see page 23, 129-130 and Fig. 1, in particular). Likewise, the ‘472 publication teaches that the CD20 CAR can comprise a leader sequence, an scFV (i.e. VL, linker, VH), a hinge/transmembrane domain, and an intracellular signaling domain (See page 16, in particular). The ‘472 publication teaches rituximab CD20 binding domains, which inherently comprise CDRs of SEQ ID NO: 17-18 of the instant claims.
The reference differs from the claimed invention in that it does not explicitly teach the CD19 scFV of SEQ ID NO: 4 and 6, or the CD20 having CDRs of SEQ ID NO: 21 and 22.
WO 2015/187528 teaches a CD19 CAR that has a VH/VL identical to SEQ ID NO: 4 and 6 of the instant application (see SEQ ID NO: 1 of WO 2015/187528). WO 2015/187528 teaches nucleic acids encoding said CAR and that it is useful for targeting malignant B cells. WO 2015/187528 teaches that the CAR comprises a CD8 hinge/transmembrane domain, CD28, CD3 zeta chain identical to SEQ ID NO: 7-9, of the instant application. See SEQ ID NO: 1 of WO 2015/187528, which comprises, from N-C terminus, the signal peptide of SEQ ID NO: 3 of the instant application, a VL sequence 100% identical to SEQ ID NO: 4 of the instant application, a linker identical to SEQ ID NO: 5 of the instant application, a VH identical to SEQ ID NO: 6 of the instant application, a CD8/hinge identical to SEQ ID NO: 7 of the instant application, a CD28 intracellular domain 100% identical to SEQ ID NO: 8 of the instant application, and a CD3 zeta domain 100% identical to SEQ I D NO: 9 of the instant application. WO 2015/187528 teaches that said CD19 CAR has a fully human antigen binding domain (see page 24, in particular).
The ‘720 publication teaches anti-CD20 binding domains having a VH of SEQ ID NO: 46 and a VL of SEQ I DNO: 48, which are 100% identical to SEQ ID 21 and 22 of the instant application (i.e. a 2.1.2 CD20 binding domain). The ‘720 publication teaches that the binding domains can be in the form of an scFV and that the CD20 binding domains are fully human and can target CD20 malignant cells for immunotherapy (see page 1 and 11, in particular). The ‘720 publication teaches that the fully human binding domains are advantageous since they do not result in significant human anti-chimeric antibody response (see paragraph 35, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the CD19-CAR of WO 2015/187528 and the CD20 binding domain of the ‘720 publication, as the CD19-CAR and the CD20 binding domain in the CAR constructs of the ‘472 publication. The ordinary artisan would be motivated to do so with a reasonable expectation of success, since WO 2015/187528 and the ‘720 publication teach that they represent fully human binding domains, and the ‘720 publication teaches that said fully human binding domains are advantageous since they do not result in significant human anti-chimeric antibody response. Furthermore, selecting from known CD19/CD20 CAR or binding domains would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
Applicant’s arguments filed 3/27/25 have been fully considered, but they are not persuasive.
Applicant argues that because the ‘472 publication only reduces to practice and tests a CD19 and CD22 bicistronic CAR, the reference does not enable or teach a CD19 and CD20 bicistronic CAR. Applicant further argues that there is a high level of unpredictability in the art regarding CAR constructs citing Long and Alabanza as evidence.
References may be relied upon for all that they would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). The ’472 publication clearly teaches a CD19 and CD20 bicistronic CAR for the reasons of record, and provides sufficient guidance and teachings to enable making said CAR.
Regarding Long, Applicant argues that the reference cautions against using CD28 signaling domain, and embodiments of the present invention employ such CD28 signaling domains. Applicant argues Long teaches that the structural characteristics of CAR ectodomains can critically effect functionality.
As an initial matter, it is noted that claim 1 encompasses any signaling domain. Even the dependent claims only require CD28 signaling domain in one of the CAR, such as the CD19 CAR, and WO 2015/187528 explicitly reduces to practice a complete and functional CD19 CAR with CD28 signaling domains. Likewise, the ‘472 publication teaches CD19 CAR with CD28 signaling domains, and that they can be combined with CD20 CAR having CD28 or 4-1BB signaling domains. The ‘472 publication teaches a CD20 CAR within the scope of the instant claim 1 (i.e. rituxumab). Using the CD19 CAR of WO 2015/187528 as the CD19 CAR in the CAR constructs of the ‘472 publication would be predicable and could be pursued with a reasonable expectation of success. Furthermore, Long explicitly acknowledges that CD19 CAR T cells using CD28 signaling domains are effective and do not exhibit tonic signaling. Rather, T cell exhaustion in Long is found when targeting GD2 solid tumors. To the extent the teachings are even applicable to targeting B cell malignancies, Long also teaches a solution to the problem of T cell exhaustion. For example, Long explicitly teaches using 4-1BB signaling domain, ameliorates T cell exhaustion (see page 587, in particular). Thus, the ordinary artisan would have a reasonable expectation of success in expressing the CD20 CAR having a 4-1BB signaling domain, as made obvious above. As noted above, claimed CD20 CAR encompasses any signaling domain.
Regarding Alabanza, the reference teaches constructing CD19 CAR with fully human variable regions using either CD28 hinge or CD8 hinge. Both hinges were functional and the reference teaches CARs with either CD8 hinge or CD28 hinge have similar ability to eliminate established tumors. As Applicant concedes, Alabanza teaches hinges from either CD28 or CD8 hinge could be selected, as desired. It is also noted that claim 1 does not even require a hinge domain, and claim 11 encompasses any hinge. The cited references provide detailed guidance regarding CAR construction, including hinge selection, and provide a reasonable expectation of success.
Applicant further argues that because the ‘472 publication teaches certain type of CD20 sequences, and there would be no reason to use CD20 sequences from other sources, such as those taught in the other cited references.
As an initial matter, the ‘472 publication specifically teaches rituxumab as a type of CD20 binding domain, which is within the scope of claim 1 (i.e. CDRs of SEQ ID NO: 17-18). Alternatively, the ordinary artisan would also be motivated to select a human CD20 binding domain to achieve the advantages taught by the reference (i.e. avoiding significant human anti-chimeric antibody response). The ordinary artisan would have a reasonable expectation of success in doing so. For example, the ‘472 publication teaches a CD20 CAR comprising a CD20 binding domain comprising 6 CDRs, or a VH/VL pair from a CD20 antibody molecule (see paragraphs 134-136, in particular). The ‘472 publication teaches that the CD20 binding domain can be characterized by functional features or properties, such as specifically binding to human CD20 and can be a human scFV (See paragraph 141-142). There would be a reasonable expectation of success in selecting the human VH/VL sequences that bind human CD20 taught in the ‘720 publication.
Moreover, selecting from known CAR and CD20 sequences would involve simple substitution of one known element for another to obtain predictable results. Doing so would also involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
Claim 1-2, 6, 10-19, 21-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015/187528, in view of Jaspers, 2017, Fousek, 2017.
WO 2015/187528 teaches a CD19 CAR that has a VH/VL identical to SEQ ID NO: 4 and 6 of the instant application (see SEQ ID NO: 1 of WO 2015/187528). WO 2015/187528 teaches nucleic acids encoding said CAR for expression in CAR T Cells and that it is useful for targeting malignant B cells. WO 2015/187528 teaches that the CAR comprises a CD8 hinge/transmembrane domain, CD28, CD3 zeta chain identical to SEQ ID NO: 7-9, of the instant application. See SEQ ID NO: 1 of WO 2015/187528, which comprises, from N-C terminus, the signal peptide of SEQ ID NO: 3 of the instant application, a VL sequence 100% identical to SEQ ID NO: 4 of the instant application, a linker identical to SEQ ID NO: 5 of the instant application, a VH identical to SEQ ID NO: 6 of the instant application, a CD8/hinge identical to SEQ ID NO: 7 of the instant application, a CD28 intracellular domain 100% identical to SEQ ID NO: 8 of the instant application, and a CD3 zeta domain 100% identical to SEQ I D NO: 9 of the instant application.
The reference differs from the claimed invention in that it does not explicitly teach a CD20 CAR or a cleavage site.
Jaspers teaches that CD19 CAR T cells are used in cancer treatment, but that in certain cases antigen loss can drive resistance. Jaspers teaches a potential approach to overcome this includes engineering CAR T cells to express two CARs targeting two antigens (See pages 84-85 and Fig. 1, in particular). Jaspers teaches that targeting a combination of CD19 and CD20 has been proven effective (See page 84, in particular).
Fousek teaches the same problem of antigen escape via loss of CD19 and the advantages of include CAR targeting additional tumor antigens. Fousek teaches CAR T cell comprising a nucleic acid sequence for expressing three individual CAR targeting CD19, CD20, and CD22, wherein viral 2A intervening sequences (i.e. a cleavage sequence or a “modified” F2A ) are used for near equal expression of the individual CARs. Fousek teach that CAR comprise an scFV targeting domain, a transmembrane domain, and an intracellular signaling domain of 4-1BB and CD3zeta. Fousek teach that the CAR T cells expressing multiple CARs killed tumor cells more robustly than CD19 CAR T Cells. Fousek teaches a rituxumab scFV CD20 binding domain, which inherently has the CDRs of SEQ ID NO: 17-18, which represent the VH and VL of rituxumab.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to further include a nucleic acid sequence encoding a CD20 CAR with a 2A cleavage site, as taught by Jaspers and Fousek, in the CD19 CAR T cells of WO 2015/187528. The ordinary artisan would be motivated to do so with a reasonable expectation of success, because Jaspers and Fousek teach that it is advantageous to avoid antigen escape and can increase tumor cell killing by CAR T cells.
Regarding the signaling domains, Fousek teaches using 4-1BB signaling domains and CD3zeta in all of the CARs, rendering this embodiment obvious. Alternatively, WO 2015/187528 teaches that CD28 could also be used in CAR signaling domains instead of, or in addition to 4-1BB, and including a CD28 signaling domain in one or more of the CARs would also be obvious.
Claim 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0362472, WO 2015/187528 and US 20070014720, as applied to claim 1 above, and further in view of US 2015/0197771.
The teachings of the ‘472 publication, WO 2015/187528 and US 20070014720 are described above.
The references differ from the claimed invention in that they do not explicitly teach SEQ ID NO: 10.
The ‘771 publication teaches an F2A cleavage peptide comprising SEQ ID NO: 35, which is identical to SEQ ID NO: 10 of the instant application. The ‘771 publication teaches that the F2A peptide can be used in an expression vector to encode a polypeptide that can be cleaved at the 2A peptide to generate separate polypeptides (see Table 3, page 9, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the F2A cleavage peptide of the ‘771 publication, as the F2A protease cleavage site in the constructs made obvious by the ‘472 publication, 2015/187528 and US 20070014720.
Doing so would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because
Applicant’s arguments filed 3/27/25 have been fully considered, but they are not persuasive.
Applicant argues that the ‘771 publication does not teach CAR constructs.
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).
Claims 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over US WO 2015/187528, Jaspers, 2017, Fousek, 2017, as applied to claim 1 above, and further in view of US 2015/0197771.
The teachings of WO 2015/187528, Jaspers, Fousek, 2017 are described above.
The references differ from the claimed invention in that they do not explicitly teach and F2A peptide or SEQ ID NO: 10.
The ‘771 publication teaches an F2A cleavage peptide comprising SEQ ID NO: 35, which is identical to SEQ ID NO: 10 of the instant application. The ‘771 publication teaches that the F2A peptide can be used in an expression vector to encode a polypeptide that can be cleaved at the 2A peptide to generate separate polypeptides (see Table 3, page 9, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the F2A cleavage peptide of the ‘771 publication, as the F2A protease cleavage site in the constructs made obvious by the other cited references.
Doing so would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because
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.
Claims 1-4, 6, 10-19, 21-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 13 of U.S. Patent No. of 10,287,350, in view of US 2016/0362472, US 2015/0197771, and US 20070014720 OR in view of Jaspers, 2017, Fousek, 2017.
The ‘350 patent claims a nucleic acid sequence encoding a CAR of SEQ ID NO: 1, and a cell expressing a vector comprising said CAR, and the use of said cells to treat B cell malignancy in a subject (i.e. as pharmaceutical composition). Said SEQ ID NO: 1 is identical to the CD19 scFV CAR encoded by residues 1-502 of SEQ ID NO: 20 of the instant application, and thus comprises the VH and VL of SEQ ID NO: 4 and 6, and a CD8 hinge/transmembrane domain, CD28, CD3 zeta chain identical to SEQ ID NO: 7-9, of the instant application. Said SEQ ID NO: 1 also comprises a signal peptide of SEQ ID 3 of the instant application, and a linker identical to SEQ ID NO: 5 of the instant application. Although the ‘350 patent does not specifically claim a second CAR encoded from the same nucleic acid, it would be obvious to encode a second CD20 CAR using a bicistronic cleavage site as taught by the ‘472 publication to allow targeting of multiple different antigens. Furthermore, the other recited sequences are obvious based on the teachings of the ‘472 publication, the ‘720 publication, and the ‘771 publication for the same reasons set forth above. Alternatively, it would be obvious to include a CD20 CAR having a rituxumab binding domain as taught by Jaspers and Fousek for the same reasons set forth above.
Applicant’s arguments filed 3/27/25 have been fully considered, but they are not persuasive.
Applicant argues that the claims are not obvious for the same reasons set forth above.
Claims 1-4, 6, 10-19, 21-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. of 11,236,161, in view of US 2016/0362472, US 2015/0197771, and US 20070014720 OR in view of Jaspers, 2017, Fousek, 2017.
The ‘161 patent claims a method of treating B cell malignancy comprising administering a T cell comprising a vector comprising a nucleic acid sequence encoding a CD19 CAR of SEQ ID NO: 1. Said SEQ ID NO: 1 is identical to the CD19 scFV CAR encoded by residues 1-502 of SEQ ID NO: 20 of the instant application, and thus comprises the VH and VL of SEQ ID NO: 4 and 6, as well as SEQ ID NO: 3, 5, and 7-9 of the instant application. Although the ‘161 patent does not specifically claim a second CAR encoded from the vector, it would be obvious to encode a second CD20 CAR using a bicistronic cleavage site as taught by the ‘472 publication to allow targeting of multiple different B cell antigens. Furthermore arriving the other recited sequences is obvious based on the teachings of the ‘472 publication, the ‘720 publication, and the ‘771 publication for the same reasons set forth above. Alternatively, it would be obvious to include a CD20 CAR having a rituxumab binding domain as taught by Jaspers and Fousek for the same reasons set forth above.
Applicant argues that the claims are not obvious over the cited references for the same reasons set forth above.
The claims stand rejected for the reasons set forth above.
Claims 1-4, 6, 10-19, 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 17/557,845, or claims 1-45 of application 17/696,249 , in view of in view of US 2016/0362472, US 2015/0197771, and US 20070014720 OR in view of Jaspers, 2017, Fousek, 2017.
The claims of the copending application claim a CD19 CAR of SEQ ID NO: 1. Said SEQ ID NO: 1 is identical to the CD19 scFV CAR encoded by residues 1-502 of SEQ ID NO: 20 of the instant application, and thus comprises the VH and VL of SEQ ID NO: 4 and 6, as well as SEQ ID NO: 3, 5, and 7-9 of the instant application. Although the applications do not specifically claim a second CAR encoded from a vector, it would be obvious to encode a second CD20 CAR using a bicistronic cleavage site as taught by the ‘472 publication to allow targeting of multiple different B cell antigens. Furthermore, the other recited sequences are obvious based on the teachings of the ‘472 publication, the ‘720 publication, and the ‘771 publication for the same reasons set forth above. Alternatively, it would be obvious to include a CD20 CAR having a rituxumab binding domain as taught by Jaspers and Fousek for the same reasons set forth above.
Applicant argues that the claims are not obvious over the cited references for the same reasons set forth above.
The claims stand rejected for the reasons set forth above.
Claims 1-4, 6, 10-19, 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of copending Application No. 18/282,919.
The ‘919 application claims a nucleic acid encoding a first CAR and a second CAR with a cleavage sequence position between the first and second CAR. The ‘919 application claims said nucleic acid sequence encodes SEQ ID NO: 71, which encodes a first CAR identical to that of the instant claim (i.e. having the same leader, CD19scFV, transmembrane/hinge, CD28 intracellular and CD3 zeta signaling domain sequences), and the identical CD20scFV, 4-1BB, and CD3 signaling domain sequences of the instant claims. Said SEQ ID NO: 71 further comprises the cleavage sequence of SEQ ID NO: 10.
No claim is allowed.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644