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 .
Claims 1-18 are pending and are under examination.
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 2-18 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.
Claims 2-17 recites the limitation "the mammalian synthetic chromosome" in line 1 There is insufficient antecedent basis for this limitation in the claims.
Regarding claims 4-5, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 2 recites the limitation "the expression" in line 2 There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation "The cell" in line 1 There is insufficient antecedent basis for this limitation in the claim.
Claim 18 recites the limitation "the cell" in line 1 There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1-2, 4-5, 10-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/115906, in view of Kazuki, 2011, and WO 2017/180665.
WO 2018/115906 teaches T cells (i.e. a leukocyte) that have been engineered to express nucleic acids encoding more than one different CAR specific for a malignant cells (see page 2-3, in particular). WO 2018/115906 teaches pharmaceutical compositions of said T cells for treating cancer (i.e. a composition with an additive, see page 3 and 9, in particular). WO 2018/115906 teaches that the T cells are engineered by introducing one or more (or two or more) nucleic acids encoding the CAR (see page 8-9, 19, in particular). WO 2018/115906 also teaches that the T cells can further be modified with a nucleic acid sequence encoding a suicide gene, such as an inducible caspase, and that the nucleic acid sequence may be introduced to the T cells together with the nucleic acid encoding the CAR, i.e. an inducible safety switch, see page 25-26, in particular. WO 2018/115906 teaches that the T cells can be engineered to express a CD3 CAR, a CD5 CAR, and a CD7 CAR, and also teaches that the T cell can express 5 or more nucleic acid sequences encoding the CAR, for example, wherein each nucleic acid sequence may encode different CD3 CARs (See pages 1-3 and 29, in particular). WO 2018/115906 teaches using the PGK promoter, i.e. a constitutive promoter, for CAR expression (see examples). WO 2018/115906 teaches the nucleic acids are introduced by transfection with a human artificial chromosome (i.e. a synthetic mammalian chromosome) comprising the nucleic acids (See pages 23-24, in particular). In other words, the reference teaches a human artificial chromosome for use as a composition to engineer the T cell, wherein the human artificial chromosome comprises a nucleic acid sequence encoding an inducible safety switch and two or more nucleic acid sequences (such as 5 or more) encoding different CARs.
WO 2018/115906 does not explicitly teach the features of the human artificial chromosome, but does teach using human artificial chromosomes as described in Kazuki, 2011.
Kazuki teaches that human artificial chromosomes exhibit characteristics that are ideal as a gene delivery vector, including stable episomal maintenance and capacity to carry large genomic loci (see page 1591, in particular). Kazuki teach human artificial chromosomes have a centromere and that they can be generated de novo, such as in HT1080 cells, and using transfected DNA, i.e. rDNA (See pages 1592 and 1594-1595, in particular). Kazuki teaches that transgenes expressed in human artificial chromosomes can be surrounded with insulators to protect from positional effects of neighboring sequences (see page 1592, in particular). Kazuki teaches that the human artificial chromosomes comprise cloning sites for inserting exogenic genes, wherein the chromosome comprises multiple copies of a single recombination acceptor site (see page 1593 and Table 1, in particular). Kazuki teach that the artificial chromosomes can express transgenes using a variety of promoters, inducible or constitutive, see page 1596, in a particular).
See also WO 2017/180665 which teaches human synthetic/artificial chromosomes for use in delivery of multiple genes to a recipient cell, wherein chromosome comprises an rDNA amplified centromeric region, multiple copies of a site specific recombination site, such as att, i.e. multiple copies of a single recombination site (see paragraphs 53-54, examples, and claims, in particular). WO 2018/115906 teaches synthetic chromosomes have advantages over other nucleic acid delivery systems that include increased payload size and that they avoid potential host-cell disruption and immunological complications (see page 2, in particular). WO 2018/115906 teaches that artificial chromosomes are useful as a delivery vehicle to deliver one or more genes that enhance immune cell activation, growth, or increases specificity to developing tumors, such as factors that increase homing or immune cell binding to specific tumor markers (see paragraphs 11, 47 and claims, in particular). WO 2017/180665 teaches that an inducible or constitutive promote could be used depending on the desired expression control.
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 human artificial/synthetic chromosomes as taught by Kazuki and WO 2017/180665, as the human artificial chromosomes for delivery CARs of WO 2018/115906. 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 references teach that they have advantages such as increased payload size, they avoid potential host-cell disruption and immunological complications, and they exhibit stable episomal maintenance. Furthermore, WO 2017/180665 teaches that the artificial chromosomes are useful as a delivery vehicle to delivery one or more genes that enhance immune cell activation, growth, or increases specificity to developing tumors, such as factors that increase homing or immune cell binding to specific tumor markers.
Claims 3, 6-9 is rejected under 35 U.S.C. 103(a) as being unpatentable over WO 2018/115906, in view of Kazuki, 2011, and WO 2017/180665, as applied to claims 1 above, and further in view of WO2016126608.
The combined teachings of WO 2018/115906, Kazuki, and WO 2017/180665 are discussed above.
They do not explicitly teach one more chemokine receptors or CAR specific to the tumor associated antigens from claim 3.
WO2016126608 teaches immune cells engineered to express multiple different CAR, wherein the first CAR can be expressed from a constitutive promoter and a second CAR is expressed using a conditional (i.e. inducible) promoters. WO2016126608 teaches that the first CAR can be specific for EGFR, and the second CAR can bind to mesothelin (i.e. EGFR and MSLN, as recited in claim 3, see page 3, in particular). WO2016126608 teaches that doing so is advantageous since it avoids tumor escape due to loss of a first tumor antigen. WO2016126608 also teaches that CAR T cells can be further engineered to express chemokine receptors that recognize chemokines secreted by tumors to improve CAR homing (See pages 138-139, in particular).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of WO2016126608, to the artificial chromosomes constructs made obvious by WO 2018/115906, of Kazuki, and WO 2017/180665. One of ordinary skill in the art at the time the invention was made would have been motivated further include a nucleic acid encoding a chemokine receptor under the control of a promoter to improve CAR homing for tumor targeting. Furthermore, one of ordinary skill in the art at the time the invention was made would also have been motivated use CAR targeting EGFR and MSLN, with a constitutive and inducible promoter (which also meets the limitation of claims 7-9), since WO2016126608 teaches that doing so is advantageous to target particular types of tumors and to avoid tumor escape due to loss of a first tumor antigen. Additionally it is noted that choosing between inducible or constitute promoters for any of the elements (i.e. chemokine receptor, safety switch, or CAR) could be optimized to achieve a desired expression pattern.
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 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,559,567, in view of WO 2018/115906, Kazuki, 2011, and of WO2016126608.
The ‘567 patent claims a mammalian synthetic chromosome comprising a centromeric sequence amplified by rDNA, multiple copies of a site specific recombination site, and at least two heterologous genes loaded into the recombination sites, wherein the synthetic chromosome is in an isolated immune cell, and there the synthetic chromosome offers increased immune cell function. It would be obvious to include nucleic acids encoding multiple CARs, as the heterologous genes, since WO 2018/115906 and WO2016126608 teaches that they improve immune cell function in treating cancer. The ordinary artisan would have a reasonable expectation of success in doing so, since WO 2018/115906 teaches that CAR can be introduced via artificial chromosomes. Furthermore, it would be obvious to include a chemokine receptor, safety switch, inducible/constitute promoters and CAR targeting EGFR and MSLN based on the teachings of the cited references for the same reason set forth above. Any other features of the artificial chromosome, such as in insulator would also be obvious based on Kazuki.
Claims 1-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,692,196, in view of WO 2018/115906, Kazuki, 2011, and of WO2016126608.
The ‘196 patent claims a mammalian synthetic chromosome used to express multiple genes in a host immune cell, wherein the synthetic chromosome comprises multiple site specific integration sites and wherein the multiple genes include those that increase specificity of immune cells for developing tumors. It would be obvious to include nucleic acids encoding multiple CARs, as the heterologous genes, since WO 2018/115906 and WO2016126608 teaches that they improve immune cell function in treating cancer. The ordinary artisan would have a reasonable expectation of success in doing so, since WO 2018/115906 teaches that CAR can be introduced via artificial chromosomes. Furthermore, it would be obvious to include a chemokine receptor, safety switch, inducible/constitute promoters and CAR targeting EGFR and MSLN based on the teachings of the cited references for the same reason set forth above. Any other features of the artificial chromosome, such as in insulator, centromere would also be obvious based on Kazuki.
Claims 1-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/685,905, in view of WO 2018/115906, Kazuki, 2011, and of WO2016126608.
The ‘905 application claims a mammalian synthetic chromosome comprising two or more nucleic acids encode two or more chemokine receptors and having one constitutive promoter and one inducible promoter, one or more insulators, and a leukocyte comprising said chromosome and compositions thereof with an additive. It would be obvious to further include multiple CAR nucleic acids since WO2016126608 teaches that they can be combined with chemokine receptors to increase efficacy in tumor targeting. The ordinary artisan would have a reasonable expectation of success in doing so, since WO 2018/115906 teaches that CAR can be introduced via artificial chromosomes. Furthermore, the further limitations regarding the features of the artificial chromosome (centromere, rDNA, recombinant acceptor sites) are obvious based on the teachings of Kazuki. It would also be obvious to further include an inducible safety switch as taught by WO 2018/115906.
This is a provisional nonstatutory double patenting rejection.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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