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 .
This amendment is in response to an amendment filed 1/23/2026.
Claims 1, 33, 42, 55, 56, 69, 70, 72, 75, 106, 107, 124, 131, 132, 141, 142, 152, 154 and 157-160 are pending. Claims 56, 69, 70, 72, 75, 106, 107, 124, 131, 132, 141, 42, 152 and 154 are withdrawn as drawn to non-elected subject matter. Therefore, claims 1, 33, 42, 55 and 157-160 are under examination.
This application claims benefit as a 371 filing of PCT/US2019/017727 filed 2/12/2019 which claims benefit of U.S. Provisional Application No. 62/629,593, filed February 12, 2018; U.S. Provisional Application No. 62/658,307, filed April 16, 2018; International Patent Application No. PCT/US2018/027783, filed April 16, 2018; and U.S. Provisional Application No. 62/746,895, filed October 17, 2018.
Disclosure of an immune cell comprising both a bispecific CAR and a BiTE is not found until application 62/658307 filed April 16, 2018 (¶0034 and 0115). However, claims directed to IgK signal peptides do not have support until PCT/US2019/017727 filed 2/12/2019. Hence, claims 1, 42, 55 and 157-160 have an effective filing date of 2/12/2019. SEQ ID NO:100 is not found until the instant application and thus claim 33 has an effective filing date of 8/11/2020.
Response to Amendments
Applicants’ amendment is sufficient to overcome the previous rejection under 35 USC 102. A search of the art demonstrated that use of Igk signal peptides in such constructs was well known in the art and hence new art necessitated by amendment has been set forth below.
Information Disclosure Statement
An information disclosure statement filed 1/23/2026 has been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 33, 55 and 157-160 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The term “cells” defined by the specification at ¶0345 are used for in vivo delivery and hence the cells can be in a human and in the broadest terms read on a human comprising the cell. The nucleic acid according to the dependency reads on apparently the sequence in the cells used in vivo. These sequences and compositions as part of the cell composition will be found in the human. The scope of the claims, therefore encompasses a human being, which is non-statutory subject matter. As such, the recitation of the limitation “non-human” or “isolated” would be remedial. See 1077 O.G. 24, April 21, 1987. This rejection is maintained for reasons below but extended to newly added claim 160.
Response to Arguments
Applicants argue that the claim does not read on a cell and importing language from the disclosure is not proper. However, the disclosure teaches that the immune cells are used to treat subjects and hence the cell is administered to the subject.
[Abstract] In another aspect, the invention features a method of treating a cancer in a subject in need thereof, the method comprising administering the immune cell.
[0080] As used herein, a “subject” means a human or animal.
This is not importing limitations into the claims but providing the broadest reasonable interpretation of the invention based upon the disclosure. Guidance provided to examiners is
In this situation, a rejection under 35 U.S.C. §101 based upon the reasoning that the claims read on a whole animal and therefore on a human being (non-statutory subject matter) may be appropriate. This particular situation is independent of whether or not there is hand of man. If the cell would reasonably read upon a human embryo or whole human, or is inseparable therefrom, it would be rejected as non-statutory regardless of whether there was something in the claim that was not derivable from nature. Such a rejection should clearly identify where in the specification the cell is defined in such a manner that it would reasonably read on a human embryo or animal. This particular rejection can be obviated by the amendment of the claims to specify that the cells are “non-human.”
Once the cell is in vivo, it encompasses the entire human. This is distinct from rejecting the claims for not falling into one of the categories of statutory matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis 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.
Claims 1, 42, 55, 159 and 160 are rejected under 35 U.S.C. 103 as being unpatentable over Bonifant and Gottschalk (U.S. application 20190307799) in view of Balyasnikova and Lesniak (U.S. Patent 10,851,169). This is a new rejection necessitated by applicants’ amendment.
Bonifant and Gottschalk teach a nucleic acid vector encoding CAR and bispecific engagers. This bispecific engager is a molecule that binds to an immune cell i.e. a T cell and a second portion that binds to a target antigen (see ¶ 0005, 0008, 0010).
[0010] In some embodiments, provided herein are engineered lymphocytes comprising: (a) a first polynucleotide sequence encoding bispecific engager molecule that comprises an antigen-recognition domain capable of binding a first antigen and an activation domain capable of binding a molecule moiety displayed on T cells that activates an immunomodulatory signal upon binding
This is ultimately a BiTE which is defined in the instant disclosure as a molecule that binds to a T cell and to a target antigen.
(instant abstract) In one aspect, the invention features an immune cell engineered to express: (a) a chimeric antigen receptor (CAR) polypeptide including an extracellular domain including a first antigen binding domain that binds to a first antigen and a second antigen-binding domain that binds to a second antigen; and (b) a bispecific T cell engager (BiTE), wherein the BiTE binds to a target antigen and a T cell antigen. CAR and the bispecific engager (which is based upon the description by Staple a BiTE) are co-expressed on a single vector (see ¶0096-0097).
Missing from the teachings is that the CAR is a tandem CAR with two antigen binding domains. However, to treat CLL (¶0094), Engels teaches use of two antigen binding domains (i.e. see figure 41A) wherein two can be IL-13ra2 and EGFRviii (see e.g. ¶0139).
Further missing from the teachings is that the BiTE is linked to an Igk signal peptide. However, linkage of signal peptides especially an Igk signal peptide was shown in the art to be routine as shown by Balyasnikova and Lesniak (see claim 9).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to use the tandemly arranged CAR of Engels et al in place of the single CAR of the composition of Bonifant and Gottschalk and to append the BiTE with an Igk signal peptide. Such a modification would have resulted in a compositions encompassed by claims 1, 42, 55, 159 and 159. As noted above: 1) Bonifant and Gottschalk teach use of CAR in combination with bispecific engagers for more effective cancer therapy; 2) Engels et al teach the same cancer therapy is benefited by use of a tandem CAR directed against IL-13ra2 and EGFRviii. It is known in the art that targeting two antigens is beneficial as evidenced by Rabinovich (¶0126).
Tandem CARS may be more effective in killing cancers expressing low levels of each antigen individually and may also reduce the risk of tumor immune escape due by single antigen loss variants Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the expanded composition would allow improved treatment.
Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the expanded composition would allow improved treatment.
3) Hence, to the construct above, Balyasnikova and Lesniak teach appendage of an Igk signal peptide which is well known to be used to efficiently localize expressed sequences by entering the secretory pathway. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the appended construct would be improved for expression
The composition of each of the references is used as a pharmaceutical and polynucleotides encoding thereof as recited in instant claim 42 (see e.g. Bonifant and Gottschalk, ¶0104).The sequence is introduced and is therefore heterologous as recited in claim 160.
Claim 157 and 158 are rejected under 35 U.S.C. 103 as being unpatentable over Bonifant and Gottschalk (US 20190307799) in view of Engels (US 20190375815) as evidenced by Rabinovich (US 20160151491) as applied to claims 1, 42, 55, 157 and 159 above, and further in view of Chaudhary (US 20190112380). This is a new rejection necessitated by applicants’ amendment.
For use in linking CAR to other molecules and hence producing polyproteins, it is shown in the art that 2A, a cleavable linker, is a known tool to do so (see Chaudhary, ¶00342).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to arrange the bispecific engager and the CAR of Engels et al with a cleavable linker as taught by Chaudhary. Such a modification would have resulted in a compositions encompassed by claim 33. As noted above: 1) Bonifant and Gottschalk teaches use of CAR in combination with bispecific engagers for more effective cancer therapy; 2) Engels et al teach the same cancer therapy is benefited by use of a tandem CAR directed against IL-13ra2 and EGFRviii and 3) Balyasnikova and Lesniak teach appendage of an Igk signal peptide which is well known to be used to efficiently localize expressed sequences by entering the secretory pathway and 4)Chaudhury et al teach use of cleavable linkers with CAR systems. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the composition would have linkers that are known to operate as desired.
Conclusion
Claim 33 is free of the art but stands rejected under 35 USC 101.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1631
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