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 .
Detailed Action
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-20 in the reply filed on 03/27/2025 is acknowledged.
Claims 21-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/27/2025.
Priority
The present application is a CIP of a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2021/019806 filed 02/26/2021.
Applicant' s claim for the benefit of a prior-filed parent provisional application 62982847, filed on 02/28/2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
The earliest possible priority for the instant application is 02/28/2020.
Claims Status
Claims 2 and 21-25 are canceled and claims 1, 3-20, and 26-27 have been considered on the merits. All arguments have been considered.
Withdrawn Objections & Rejections
Applicant's response filed 04/08/2026 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 05/30/2025 are hereby withdrawn.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
Non-Compliant Amendment
The amendment to the claims filed on 04/08/2026 does not comply with the requirements of 37 CFR 1.121(c) because the claim text for the canceled claims is presented . Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
Claim Rejections - 35 USC § 103 (New)
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-9, 11, 16, 20 and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Roth et al (Nature (2018)559:405-435; as cited in the IDS filed 05/07/2024; cited previously) in view of Kriegsmann et al (BJC (2018)38-44; cited previously), Jenkins et al (Current Opinion in Chemical Engineering (2018) 22;26-33; cited previously), Li et al (PLOS one(2014)9(8) 1-10; cited previously) and Ran et al (Nature Protocols (2013)8; 2281-2308; cited previously) and as evidenced by Merriam-Webster (aggregate definition [online]. Merriam-Webster Dictionary corporation [retrieved on 07/29/2026]. Retrieved from the Internet: <https://www.merriam-webster.com/dictionary/aggregate; newly cited).
This is a new rejection required by the claim amendments, however it is substantially similar to a previous rejection.
Regarding claims 1, 4, 5, 7, 16 and 26-27: Claim 1 recites “chimeric antigen receptor”. The instant specification defines chimeric antigen receptor (CAR) as “a recombinant fusion protein that has an antigen-specific extracellular domain coupled to an intracellular domain that directs the cell to perform a specialized function upon binding of an antigen to the extracellular domain” (p8 ¶0022).
The claim recites “CART cells”. The instant claim 1 defines a CART cell as a T cell with a transgene containing a chimeric antigen receptor (claim 1).
The claims are interpreted with the definitions as stated supra.
Roth teach reprogramming human T cell function for therapeutic purposes and specificity using non-viral genome targeting (title).
Roth teach electroporation of human primary T cells with CRISPR-Cas9 ribonucleoprotein (RNP) complexes using linear dsDNA templates for homology-directed repair (HDR) (p405 col 1 para 2).
Extended data figure 9a shows the dsDNA HDR template comprises a transgene flanked by homology arms that are complementary to sequences on both sides of the cleavage site in the T cell expressed gene (TRAC), and that the transgene is inserted into EXON 1 of TRAC (p 427).
Roth confirm the transgene is specifically integrated into the cleavage site of the T cell expressed gene locus created by the Cas9 RNP in the CART cells by observing expression of the inserted transgene (Fig 4, p 408 col 1 para 1).
The T cells are cultured in XVivo15 medium with IL-2 (an ex vivo method using Xeno-free media, as evidence by XVivo15 product sheet) (p 410 col 1 para 3).
Roth replace the endogenous T cell receptor (TCR; a T cell expressed gene) by targeting the TCR-alpha constant region (TRAC) (p407 col 2 para 5), to insert engineered receptors, TCR-beta and TCR-alpha, that recognize (binds) the NY-ESO-1 tumor antigen, to generate NY-ESO-1 cells (p408 col 1 para 1).
Fig 4h shows solid tumor volume is reduced in a mouse tumor model when mice are injected with the NY-ESO-1 CART cells (Fig 4h), demonstrating the cells have activity against an antigen on a solid tumor in vivo.
While Roth teach that the 5’ and 3’ homology arms for the dsHDR template are ~300bp (Fig 4a p408), Roth do not teach the homology arms have a length of 400-1000 bp or 450-750 bp.
Li teach optimization of genome engineering with CRISPR/CAS9 (title). Li disclose increasing the length of the homology arms of the homology-directed repair template strongly enhances targeting efficiency in CRISPR/Cas9 editing systems (Abstract). Li teach that, while larger insert sizes can have reduced efficiency of genome modification, increasing the homology arm size increases modification frequency (p9/10 col 2/1 para 3/1).
Ran et al teach genome engineering using CRISPR-Cas9 (title). Ran disclose homology arms on each side of the repair template can vary in length, but are typically longer than 500 bp (p2284 col2 para 2).
It would have been prima facie obvious to one of ordinary skill in the art to adapt the methods of Roth with the teachings of Li and Ran by using longer homology arms that can improve editing efficiency of HDR templates with larger inserts.
One having ordinary skill in the art would have understood that more efficient gene editing would enable a CRISPR/Cas9 system to generate a potentially therapeutic population of modified T cells more efficiently and therefor with less expense.
One would have had a reasonable expectation of success because Ran disclose typical homology arms are longer than 500 bp and Li disclose longer homology arms are beneficial to HDR template insertion efficiency.
The teachings of Roth are discussed supra. While Roth teach a non-viral method of site-specifically inserting a transgene encoding an antigen specific extracellular domain into a T cell, however Roth do not explicitly teach that the transgene comprises a fusion protein with the antigen specific extracellular domain coupled to an intracellular domain by a transmembrane domain.
Kriegsmann teach that chimeric antigen receptor (CAR) T cells are genetically modified T cells that express a CAR directed against specific tumor antigens (abstract). Kriegsmann also teach that CART immunotherapy shows promising results in early clinical trials as an anti-cancer therapy (p38 col2 ¶1). Kriegsmann teach CARs are directed against specific cell-surface antigens (p38 col2 ¶2). Figure 1c shows a CAR comprises an antigen specific extracellular domain coupled to an intracellular domain by a transmembrane domain, and that the antigen specific extracellular domain comprises an antibody variable region (p 42).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Roth drawn to a non-viral method of site-specifically inserting a transgene encoding an antigen specific extracellular domain into a T cell by inserting a transgene comprising a fusion protein with the antigen specific extracellular domain coupled to an intracellular domain by a transmembrane domain.
One would have been motivated to modify the method of Roth to insert an antigen specific extracellular domain coupled to an intracellular domain by a transmembrane domain because Roth teach that the need for recombinant viral vectors to genetically reprogram T cells has slowed down research and clinical because of lengthy and expensive manufacturing and testing (abstract) and Kriegsmann teach CAR T cells are promising anti-cancer therapies.
One would have had a reasonable expectation of success because both methods are drawn to genetic modification of T cells and T cell receptors for the purposes of targeting tumor antigen expressing cells.
The teachings of Roth are discussed supra. While Roth teach culture in xeno-free medium (XVivo15), Roth do not teach culturing cells in the absence of serum.
Jenkins teach serum content is a significant hurdle in T cell cultivation, and that serum-free T cell cultivation will reduce potential harmful elements and simplify T cell purification steps (p29 col1 ¶2). Jenkins further teach antigen-specific T cell cultivation has been undertaken with xeno-free serum replacement (SR), resulting in comparable T cell growth kinetics with FBS and reduced risk of adventitious infectious pathogens (p29 col1 ¶2).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Roth drawn to non-viral insertion of a transgene by culturing the cells in xeno-free conditions by using SR in place of serum as taught by Jenkins. Jenkins teach that cultivation in serum-free conditions reduces potential harmful elements and simplifies T cell purifications steps.
Accordingly, one of ordinary skill in the art would have been motivated to modify the method as taught by Roth with the teachings of Jenkins for the purposes of a more efficient and protocol with reduced harmful elements.
One would have had a reasonable expectation of success because both inventions are directed to T cell cultivation under defined conditions.
Regarding claim 6: The teachings of Roth are discussed supra. Roth teach NY-ESO-1 cells are co-incubated with human melanoma cell lines and show robust killing of the target cells (Fig9n, p 427).
Regarding claim 8: The claim requires the active steps of imaging, evaluating and selecting a population of aggregated CAR T cells.
Merriam-Webster define “aggregate” as “formed by the collection of units or particles into a body, mass, or amount” (p1). An aggregate is considered to be a collection of two or more cells.
The teachings of Roth are discussed supra. Figures 1b and 2b show that the cells of Roth form aggregates and imaging the population of modified T cells identifies the aggregates (Figures 2b). Roth further teach selecting a population of the aggregated (GFP positive) cells (Figure 2).
Regarding claim 9: The teaching of Roth are discussed supra. Roth also teach electroporation of HDR template at a concentration of 2ug/ul (2000 ng/ul) (p410 col2 para 3).
Roth do not teach the double-stranded HDR template has an OD260/OD280 and/or OD260/OD230 of a specific ratio.
With regard to the OD260/OD280 and/or OD260/OD230 of the HDR template, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
The selection of a specific level of purity of the HDR template (which would result in a more accurate concentration of HDR template introduced to the target cells, and the exclusion of impurities from the target cells) clearly would have been a routine matter of optimization and experimentation on the part of the artisan of ordinary skill, said artisan recognizing that the amount and purity of the HDR template introduced to the cultured cells would have been affected by these parameters.
Regarding claim 11: The teachings of Roth are discussed supra. Roth teach a dsDNA HDR template designed to introduce an N-terminal green fluorescent protein GFP into human primary T cells to generate CD4-GFP CART cells (p405 col 1/2 para 2/1-2). Extended data figure 4 shows the HDR template, the GFP tag, is flanked by a 5’ and 3’ homology arm (p417).
Regarding claim 20: The teachings of Roth are discussed supra. Roth also teach Figure 4b, 12.3% of the non-viral genome targeted cells express the transgene NY-ESO-1, reading on the instant claim of more than 4% of the population of unmodified T cells have the transgene inserted into their genomes (p408).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Roth in view of, Jenkins, Li and Ran over claims 1, 3-9, 11, 16, 20 and 26-27 (see above), and further in view of Sjoukje et al (Nat Rev Drug Discov(2015)14(7):499-509).
This is a new rejection due to claim amendments, however is substantially similar to a previous rejection.
The teachings of Roth and Kriegsmann are discussed supra. Kriegsmann also teach the intracellular domain comprises a CD3 zeta intracellular domain (Fig 1c). Kriegsmann is silent on the nature of the transmembrane domain.
Sjoukje teach CAR intracellular domains comprise an intracellular CD3 zeta domain (Figure 1c) and that the first fusion receptors were coupled to the CD3 intracellular domain (Figure 1). Sjoukje also teach that the transmembrane domain of the CAR CD3 zeta facilitates enhanced anti-tumor function (p25 box1, Figure 1d).
It would have been prima facie obvious to one of ordinary skill in the art to adapt the methods of Roth and Kriegsmann with the teachings of Sjoukje, to include a CD3 zeta intracellular and transmembrane domain in the receptor.
One having ordinary skill in the art would have been motivated to modify the method of Roth and Kriegsmann to include a CD3 zeta intracellular and transmembrane domain because Sjoukje teach the CD3 zeta intracellular domain is one of the first intracellular domains used, and as such one of ordinary skill in the art would understand that the function of the intracellular domain is well studied and understood, and the CD3 zeta transmembrane domain facilitates enhanced antitumor function and cytokine production (p503 Box 1).
One would have had a reasonable expectation of success because the methods are drawn to genetically engineering T cells to express chimeric T cell receptors.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Roth in view of, Jenkins, Li and Ran over claims 1, 3-9, 11, 16, 20 and 26-27 (see above), and further in view of Lu et al (RNA(2003)9:1-13) and Lanoix et al (EMBP(1988)7(8)1-8).
This is a new rejection due to claim amendments, however is substantially similar to a previous rejection.
Regarding claims 12 and 13: The teachings of Roth are discussed supra. Roth also teach the double stranded HDR template is targeted to the 5’ end of the first exon of TRAC to generate NY-ESP-1 CART cells (Extended Data Figure 9a, p427). Figure 9a also teaches the HDR template sequentially comprises a 5’ (left) homology arm- the self-cleaving peptide T2A- the CAR gene (NY-ESO-1)-a 3’ (right) homology arm.
Roth do not explicitly teach a splice acceptor site 3’ adjacent to the 5’ homology arm or a poly A terminator 5’ adjacent of the 3’ homology arm (fig 9a pa 427).
Lu et al (RNA(2003)9:1-13) teach mRNA splicing invariably enhances the level of gene expression (abstract).
Lanoix et al (EMBP(1988)7(8)1-8) teach rabbit beta-globin poly A terminator directs efficient termination of transcription of polyomavirus DNA.
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to incorporate a splice acceptor and a rabbit beta-globin poly a terminator with the non-viral double-stranded HDR template taught by Roth because Lu teach mRNA splicing enhances the level of gene expression and Lanoix teach the poly A terminator directs efficient termination of transcription.
One would have been motivated to modify the method of Roth with the teachings of Lu and Lanoix to enhance the levels of correct transgene expression. One of ordinary skill in the art would understand that efficient termination of transcription reduces improperly transcribed transgenes due to read-through errors and that improved transgene expression would result in a more efficient and therefore less expensive method.
One would have had a reasonable expectation of success because the teachings are all directed to methods of transgenes expression in human cells.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Roth in view of, Jenkins, Li and Ran over claims 1, 3-9, 11, 16, 20 and 26-27 (see above), and further in view of Terrett et al (US 2018/0325955 A1).
This is a new rejection due to claim amendments, however is substantially similar to a previous rejection.
Regarding claim 17: The teachings of Roth are discussed above. Roth do not teach a guide RNA which comprises Seq ID NO: 9.
Terrett teach genome-edited cells engineered to express a chimeric antigen receptor construct (abstract). Terrett disclose the gRNA sequence Seq ID: 51, which comprises 100% sequence identity with the instant Seq ID NO:9 (p3 ¶0029).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to combine the gRNA sequence, seq ID 51, as taught by Terrett with genome editing method taught by Roth because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Combining the gRNA disclosed by Terrett with non-viral editing method of Roth would have led to predictable results with a reasonable expectation of success because both inventions teach using an gRNA to direct genome editing in the native TRAC locus of the T-cell.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable Roth in view of, Jenkins, Li and Ran over claims 1, 3-9, 11, 16, 20 and 26-27 (see above), and further in view of Phelan et al (Stem Cell Investigation (2018)5:221-4) and as evidenced by ThermoFisher (Difference Between: 96-Well Plate Bottom Shapes [online]. COMPANY:ThermoFisher [retrieved on 01/04/2026]. Retrieved from the Internet: <URL: https://www.fishersci.com/shop/products/abgene-96-well-1-2ml-polypropylene-deepwell-storage-plate/AB1127)
This is a new rejection due to claim amendments, however is substantially similar to a previous rejection.
Regarding claim 18: The teachings of Roth are discussed above. Roth do not teach culturing in round bottom culture wells or culture in a low culture volume (20% standard) of cell culture medium.
As evidenced by ThermoFisher, round bottom wells provide optimal sample recovery (p1, downloaded from the internet 01/04/2026).
Phelan teach cell culture in low volumes exhibit similar growth as traditional protocols with improved consistency (p2 col2 ¶2). Phelan further teach that low-volume multi-well setups provide a wide-range of options possible through customization.
It would have been obvious for one of ordinary skill in the art to modify the method of Roth with the teaching of ThermoFisher and Phelan, to culture cells in round bottom plates using a low culture volume.
One would have been motivated to modify the method of Roth to use round bottom plates with a low culture volume to improve optimize sample recovery and to improve consistency of cell cultures. Furthermore, one of ordinary skill in the art would recognize that culturing cells in a low culture volume would reduce the amount of reagents required for cell culture and thus decrease cost of the cell culture.
One would have had a reasonable expectation of success because one of ordinary skill in the art would know round bottom plates are commonly used for sample processing and culture of cells in suspension and that cell culture volumes would have been a matter of routine optimization based on optimization of the cell culture protocol and cell culture protocols in the art.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Roth in view of, Jenkins, Li and Ran over claims 1, 3-9, 11, 16, 20 and 26-27 (see above), and further in view of Sadelain et al (WO 2019/157454) and Zhang et al (Blood Advances (2018) 2:14;1691-1696).
This is a new rejection due to claim amendments, however is substantially similar to a previous rejection.
Regarding claim 19: The teachings of Roth are discussed above. Roth also teaches T cells are isolated from healthy human donors (p409 col 1 para 1).
Roth does not teach the T cells are autologous or allogenic T cells.
Sadelain teach novel design of T cell receptors and engineered immunoresponsive cells comprising the same (abstract). Sadelain disclose genetic modifications at the TRAC locus to permit generation of T cells expressing a chimeric antigen receptor (abstract).
Sadelain disclose the immunoresponsive cell is an autologous T cell (claims 42, 43) and that the method could advance both autologous and allogenic T cell therapies (Example 1, p76 ln 1-5).
Zhang teach allogeneic and autologous CAR-T cell therapy to treat a leukemic patient (title). Zhang disclose CAR-T studies usually use autologous CAR-T cells, however allogeneic CAR-T cells may be more robust, though could result in graft-versus-host disease (abstract).
It would have been prima facie obvious to one of ordinary skill in the art to adapt the methods of Roth with the teachings of Sadelain and Zhang to engineer autologous or allogeneic T cells.
One having ordinary skill in the art would have understood that using autologous T cells would reduce the likelihood of the patient developing graft vs host disease, while allogeneic T cells may provide a source of T-cells for those whom use of allogeneic T cells are not possible.
One would have had a reasonable expectation of success because Zhang teaches that CAR-T therapies in humans are almost always conducted with allogeneic CAR-T cells, but autologous CAR-T cell therapy results in complete remission for a patient that failed standard treatment.
Allowable Subject Matter
Claims 14-15 are allowable.
The claims recite amplifying a sequence from Seq ID NO: 1 using primer sets of Seq ID NOs:11/12 or Seq ID NOs:17/18. Primer pairs with the sequences of Seq ID NOs: 11/12 and 17/18 are free from the art.
Response to Arguments
The responses are directed to the Arguments filed 04/08/2026, all arguments have been considered.
Regarding Arguments directed to the objection:
Claim 8 has been amended to correct a grammatical error and the objection is withdrawn.
Regarding Arguments directed to 35 USC § 103:
Regarding claim 1: Claim 1 has been amended to require homology arms having a length of 450-1000 bp which overcomes the rejection as written because a specific length of homology arms was not required in the previous claim 1 and thus not addressed in the previous rejection over claim 1.
Thus the rejection is withdrawn. A new rejection is entered.
Regarding Arguments relevant to the instant action:
Applicant argues that Roth teaches genetically modified T cells and that Roth does not refer to the cells as CAR T cells.
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).
Specifically, Roth is not relied upon to specifically teach CART cells. Roth is relied upon to teach a non-viral method of site-specifically inserting a transgene into a T cell comprising a non-viral double -stranded homology-directed repair (HDR) template comprising the transgene flanked by homology arms that are complementary to sequences on both sides of a cleavage site in the T cell expressed gene.
Kriegsmann is relied upon to teach CAR-T cells, and modifying the method of Roth to insert a transgene containing a chimeric antigen receptor (CAR) gene into a T cell would be obvious in view of Kriegsmann, as discussed above.
Thus arguments against Roth in regards to CAR-T cells are unpersuasive.
Applicant argues that Li teach away from lengthening homology arms.
Li do not teach away from lengthening the homology arms. Li teach both longer and shorter homology arms and teach that both are effective for different purposes.
MPEP 2145 reads “A prior art reference that “teaches away” from the claimed invention is a significant factor to be considered in determining obviousness; however, “the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (Claims were directed to an epoxy resin based printed circuit material. A prior art reference disclosed a polyester-imide resin based printed circuit material, and taught that although epoxy resin based materials have acceptable stability and some degree of flexibility, they are inferior to polyester-imide resin based materials. The court held the claims would have been obvious over the prior art because the reference taught epoxy resin based material was useful for applicant’s purpose, applicant did not distinguish the claimed epoxy from the prior art epoxy, and applicant asserted no discovery beyond what was known to the art.)”.
While Li teach shorter homology arms are desirable for some purposes, Li also teach that longer homology arms are desirable for some purposes and there is not a teaching that longer homology arms will not work. Thus the teachings of Li is are not considered to teach away from the instant invention.
The arguments are unpersuasive.
Applicant submits there was no expectation that increasing the length of the homology arms would improve knock-in efficiency.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., improved knock-in efficiency) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Furthermore, Li disclose increasing the length of the homology arms of the homology-directed repair template strongly enhances targeting efficiency in CRISPR/Cas9 editing systems (Abstract). Li teach that, while larger insert sizes can have reduced efficiency of genome modification, increasing the homology arm size increases modification frequency (p9/10 col 2/1 para 3/1).
Thus, if an increased knock-in efficiency were a limitation of the claim, Li would read on that limitation.
The argument is unpersuasive.
Regarding claim 8: Applicant argues that “aggregation can be indicative of successful genome editing and sell health”.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., aggregation) was not required in the rejected claim(s).
Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The amendment of claim 8 require the step of selection a population of aggregated CAR T cells overcomes the rejection as written because the limitation was optional and therefore not required in rejection as written.
The argument is unpersuasive however the rejection is withdrawn in view of the claim amendments.
Regarding arguments relevant to the new rejection:
Regarding the new limitation of selecting: Figures 1b and 2b show that the cells of Roth form aggregates and imaging the population of modified T cells identifies the aggregates (Figures 2b). Roth further teach selecting a population of the aggregated (GFP positive) cells (Figure 2).
Regarding claims 10, 12-13, 17, 18 and 19: Applicant argues the claims depend on amended claim 1 on which the rejected claims depend, and thus the amendments to claim 1 overcome the rejection as written.
The argument is persuasive and the rejection is withdrawn.
Conclusion
Claims 1, 3-13 and 16-20, and 26-27 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631
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