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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 12, 2026, has been entered.
Claims 64 and 67-74 are pending and are under consideration. The elected species are SEQ ID NO: 25 as a species of CD28 transmembrane domain, SEQ ID NO: 40 as a species of CD3zeta signal transduction domain and SEQ ID NO: 29 as a species of iCasp protein.
Grounds of Rejection Maintained
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 64 and 73-74 are rejected under 35 U.S.C. 103 as being unpatentable over Cooper et al (WO 2013/074916 A1, IDS), Hoyos et al (Leukemia, 24, 1160-1170, 2010, of record) and Bertschinger et al (WO 2010/095031 A2, of record).
Cooper et al disclose a monospecific CAR comprising an scFv that binds CD19, a CD28 transmembrane domain, and a cytoplasmic domain of 4-1BB (CD137), CD27 and CD3zeta domain and an inducible caspase 9 domain and wherein the CAR is comprised in a T cell and in a composition comprising such T cells (see entire document, e.g., abstract, pages 2, 4-6, 12, 17 19 and 47, Figures and examples).
Hoyos et al disclose a monospecific CAR comprising an scFv that binds CD19, and an inducible caspase 9 domain and wherein the CAR is comprised in a T cell and in a composition comprising such T cells (see entire document, e.g., abstract, pages 1160, 1161, 1165 and 1168 and figures).
Bertschinger et al teach an antigen-binding domain comprising the instant SEQ ID Nos: 11 and 12 that binds CD19, designated FMC63 and teach that an antibody comprising antigen-binding domain comprising the variable domains given in instant SEQ ID Nos: 11 and 12 was able to kill transplanted tumor cells (see entire document, e.g., abstract, pages 3 and 63 and see sequences 1, 2 and 69).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to make a monospecific CAR comprising an scFv that binds CD19, a CD28 transmembrane domain, and a cytoplasmic domain of 4-1BB (CD137), CD27 and CD3zeta domain and an inducible caspase 9 domain and wherein the CAR is comprised in a T cell and in a composition comprising such T cells, since T cells expressing inducible caspase 9 gene have an advantage that allows for induction of apoptosis in the T cells expressing the CAR to provide safety (see Hoyos et al, Pg. 1168, right column) and use the antibody of Bertschinger et al in the CAR constructs suggested above because each component of the CAR has been taught to be a domain that can be used in a CAR, taught as a domain that binds CD19 or taught to provide a safety switch to eliminate the T cells expressing the CAR, so such constructs would be considered to be combining prior art elements according to known methods to yield predictable results. Notably, the antigen binding domain of an antibody comprising the instant SEQ ID Nos: 11 and 12 was shown to target tumor cells as evidenced by Bertschinger et al, so that antibody would have been predictably selected as providing a CD19 antigen-binding domain that could be used in the CD19 CARs of the prior art. By way of further explanation, one of skill in the art would recognize that the CD19 antigen-binding domain of Bertschinger et al could be used in making CD19 CAR constructs, which were desirable to target CD19 expressing cancers, as evidenced by the prior art, so using the Bertschinger et al antibody would be considered to be combining prior art elements according to known methods to yield predictable results. While other CD19 antibodies would also yield such predictable results in a CD19 CAR, the FMC63 was a known antibody that would be expected to yield predictable results in targeting CD19. As genetic engineering techniques to make CARs were known as evidenced by the references, and the prior art included each element claimed, one of skill in the art could have combined the elements using such genetic engineering techniques, and the elements would be predictably expected to perform the functions in the CAR as disclosed when combined, so the rejection meets the requirements set forth in MPEP ¶ 2141 and 2143. Furthermore, as the FMC63 antigen-binding domain was known to be able to target tumor cells expressing CD19, there was an advantage to using such an antigen-binding domain comprising the instant SEQ ID Nos: 11 and 12 because the FMC63 antigen-binding domain had been studied in the art to treat cancer.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
In the response, Applicant traverses the rejection and argues that:
“The rejection over the combination of cited references must be withdrawn because the Examiner has done no more than identify the individual claim elements in the cited art without articulating any reason why a person of ordinary skill in the art would have specifically selected the specific monospecific CD19 antibody recited in the pending claims from among the myriad antibodies disclosed in Bertschinger and incorporated it into the CAR-T architecture of Cooper or Hoyos. Cooper and Hoyos generally describe CAR-T cells employing antibodies that bind CD19 but are structurally distinct from the monospecific antibody recited in pending claim 1, and Bertschinger merely lists the sequence of the antibody recited in the pending claims among several antibodies directed to CD19. The Federal Circuit and the MPEP are clear that this kind of element-by-element mapping is legally insufficient. As MPEP § 2143 explains, "the mere fact that all the claimed elements or steps appear in the prior art is not sufficient to establish a prima facie case of obviousness," and "rejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness."
In response, these arguments are not found persuasive because the rejection provides an articulated reasoning that the that results flowing from the combination would have been predictable to a person of ordinary skill in the art as set forth in MPEP § 2143. Here, the antigen-binding domain of Bertschinger et al was known to bind to CD19 and the art taught that an antibody with the antigen-binding domain of Bertschinger et al bound to tumor cells expressing CD19, such that one would have reasonably expected that using the antigen-binding domain of Bertschinger et al in CD19 CARs would have the desired effect of predictably binding tumor cells expressing CD19. Furthermore, while other CD19 antibodies were known, that may have also been used in CD19 CAR constructs, MPEP § 2143 and the MPEP in general does not require “specifically selecting the specific monospecific CD19 antibody recited in the pending claims from among the myriad CD19 antibodies” as argued by Applicant. The antigen-binding domain of Bertschinger et al would have been expected to predictably bind CD19 in CAR constructs as encompassed by the claims and the rejection provides sufficient reasoning to establish the claimed CAR constructs would have been obvious. These other myriad of CD19 antibodies may also have been obvious to include in a CAR constructs, but these other antibodies are not at issue here.
Notably, the anti-CD19 antibody FMC63 binding domain had been used in the prior art CAR of Jensen (US 2012/0301447 A1, of record) (see page 6) and had been used in a CAR in the prior art of Kochenderfer et al (J Immunother. 2009 September; 32(7):689-702, pages 1-26, of record) (see page 3), so it is evident that the prior art expected the naive anti-CD19 antibody FMC63 binding domain could be used in functional CAR constructs.
Applicant further argues that:
“Without that articulated reason for the specific selection of the combination of structural features recited in the pending claims, the rejection rests on impermissible hindsight reconstruction of the claimed invention from Applicant's own disclosure.”
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In this case, the rejection only takes into account knowledge which was within the level of ordinary skill at the time the claimed invention was made, and these domains are selected for inclusion in CAR constructs as they predictably provide known functions to the CAR constructs as evidenced by the references, so the rejection does not rest on impermissible hindsight reconstruction. Notably, Applicant has not established or argued that one of ordinary skill in the art could not have combined the elements as claimed by known methods, and that in combination, each element would not perform the same function as it does separately or that one of ordinary skill in the art would not have recognized that the results of the combination were predictable.
Accordingly, after careful and complete consideration of Applicant’s response and the record as a whole, this rejection is being maintained.
Claims 67, 69 and 72 are rejected under 35 U.S.C. 103(a) as being unpatentable over Cooper et al (WO 2013/074916 A1, IDS), Hoyos et al (Leukemia, 24, 1160-1170, 2010, of record) and Bertschinger et al (WO 2010/095031 A2, of record), as applied to claims 64 and 73-74 above, in further view of Chang et al (WO 2015/179801 A1, of record).
The previous combination teaches and suggests that which is set forth in the above 103 rejection.
Chang et al teach a using a chimeric antigen receptor (CAR) composition related CD28 region in CARs comprising the instant SEQ ID NO:25 (see entire document, e.g., abstract and see SEQ 13), a CD27 region comprising the instant SEQ ID NO:38 (see entire document, e.g., abstract and see SEQ 16) and an FKBP sequence comprising the instant SEQ ID NO:30 (see entire document, e.g., abstract and see SEQ 29).
In this case, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to use the sequences of Chang in the CAR constructs suggested above because one of skill in the art would recognize that the sequences of Chang has been used in CAR constructs before, so using the sequences of Chang would be considered to be combining prior art elements according to known methods to yield predictable results.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
In the response, Applicant traverses the rejection for the reasons set forth above.
These arguments are not found persuasive with respect to the other references as detailed above and incorporated herein.
Accordingly, after careful and complete consideration of Applicant’s response and the record as a whole, this rejection is being maintained.
Claim 68 is rejected under 35 U.S.C. 103(a) as being unpatentable over Cooper et al (WO 2013/074916 A1, IDS), Hoyos et al (Leukemia, 24, 1160-1170, 2010, of record) and Bertschinger et al (WO 2010/095031 A2, of record), as applied to claims 64 and 73-74 above, in further view of June et al (WO 2012/079000 A1, of record).
The previous combination teaches and suggests that which is set forth in the above 103 rejection.
June et al teach a using a 4-1BB sequence comprising the instant SEQ ID NO:42 in CARs (see entire document, e.g., abstract and see SEQ 23).
In this case, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to use 4-1BB sequence of June in the CAR constructs suggested above because one of skill in the art would recognize that the 4-1BB sequence of June has been used in CAR constructs before, so using the 4-1BB sequence of June would be considered to be combining prior art elements according to known methods to yield predictable results.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
In the response, Applicant traverses the rejection for the reasons set forth above.
These arguments are not found persuasive with respect to the other references as detailed above and incorporated herein.
Accordingly, after careful and complete consideration of Applicant’s response and the record as a whole, this rejection is being maintained.
Claim 70 is rejected under 35 U.S.C. 103(a) as being unpatentable over Cooper et al (WO 2013/074916 A1, IDS), Hoyos et al (Leukemia, 24, 1160-1170, 2010, of record) and Bertschinger et al (WO 2010/095031 A2, of record), as applied to claims 64 and 73-74 above, in further view of Sadelain et al (US 2004/0043401 A1, of record).
The previous combination teaches and suggests that which is set forth in the above 103 rejection.
Sadelain et al teach a using a CD3zeta sequence comprising the instant SEQ ID NO:40 in CARs (see entire document, e.g., abstract and see SEQ 14).
In this case, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to use said CD3zeta sequence in the CAR constructs suggested above because one of skill in the art would recognize that said CD3zeta sequence has been used in CAR constructs before, so using said CD3zeta sequence would be considered to be combining prior art elements according to known methods to yield predictable results.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
In the response, Applicant traverses the rejection for the reasons set forth above.
These arguments are not found persuasive with respect to the other references as detailed above and incorporated herein.
Accordingly, after careful and complete consideration of Applicant’s response and the record as a whole, this rejection is being maintained.
Claim 71 is rejected under 35 U.S.C. 103(a) as being unpatentable over Cooper et al (WO 2013/074916 A1, IDS), Hoyos et al (Leukemia, 24, 1160-1170, 2010, of record) and Bertschinger et al (WO 2010/095031 A2, of record), as applied to claims 64 and 73-74 above, in further view of Brenner et al (WO 2011/146862 A1).
The previous combination teaches and suggests that which is set forth in the above 103 rejection.
Brenner et al teach a using a caspase sequence comprising the instant SEQ ID NO:29 in T cells as a suicide gene (see entire document, e.g., abstract and see SEQ 9).
In this case, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to use said caspase sequence in the CAR constructs suggested above because one of skill in the art would recognize that said caspase sequence has been used in T cells before as a suicide gene, so using said caspase sequence would be considered to be combining prior art elements according to known methods to yield predictable results.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
In the response, Applicant traverses the rejection for the reasons set forth above.
These arguments are not found persuasive with respect to the other references as detailed above and incorporated herein.
Accordingly, after careful and complete consideration of Applicant’s response and the record as a whole, this rejection is being maintained.
Conclusion
No claims are allowed. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kochenderfer et al (J Immunother. 2009 September; 32(7):689-702, pages 1-26, of record) disclose CD19 chimeric antigen receptors made using sequences from antibody FMC63 (see page 3). Jensen (US 2012/0301447 A1, of record) disclose CD19 chimeric antigen receptors made using sequences from antibody FMC63 (see page 6).
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 CFR 1.114 and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner can normally be reached on Monday through Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
August 28, 2026
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