DETAILED ACTION
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 .
Priority
This application is a U.S. national phase of International Application No. PCT/US20/61944, filed on 11/24/2020, which claims domestic benefit to US provision application 62/942,770, filed 12/03/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
The Amendment, filed on 11/15/2025, is acknowledged in which:
Claims 6-10, 14-18, 28-49, and 51-123 are canceled.
Claims 1, 4-5, 19, 26-27, and 50 are currently amended.
Claims 11 and 20-25 were previously presented.
Claims 2-3 and 12-13 are original.
Claims 1-5, 11-13, 19-27, and 50 are pending in the instant application and are examined on the merits herein.
Withdrawn Objections and Rejections
In the office action dated 8/11/2025,
The specification was objected to for informalities in the text and missing symbols indicating trade names or marks used in commerce. Applicant’s submission of an amended specification with appropriate corrections has overcome the objections and the objections are withdrawn.
Claim 19 was objected to for a typographical error. Applicant’s amendment to the claim has overcome the objection and the objection is withdrawn.
All previous rejections of claims 6 and 9 are rendered moot in view of claim cancellations.
Claims 1-5, 11-13, 19-23, 25-27, and 50 were rejected under 35 USC 102(a)(1) as being anticipated by Wu. Applicant’s amendment to the base claim to recite optogenetic dimerizer pair selected from CRY2/CIBN pair, CRY2/SPA1 pair, or CRY2/BIC1 pair has overcome the rejections and the rejections are withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Wu and Kennedy as discussed below.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5, 11-13, 19-27, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/127261 A1 (herein Wu) and Kennedy (Nat Methods. 2010;7(12):973-975).
Wu teaches an isolated nucleic acid sequence or sequences that encode heterodimeric, conditionally active chimeric antigen receptor (CAR) (¶ [0060]-[0061]), comprising:
a first polypeptide comprising (i) an antigen binding domain, (ii) a first modulatory domain (e.g. costimulatory domain), (iii) first member of a dimerization pair, and (iv) a transmembrane domain interposed between the antigen-binding domain (i) and the first modulatory domain (ii) (i.e. “Component I” of the instant claim); and
a second polypeptide comprising (i) a transmembrane domain, (ii) a second modulatory domain (e.g. costimulatory domain), (iii) a second member of the dimerization pair, and (iv) an intracellular signaling domain. (i.e. “Component II” of the instant claim) (¶ [0062]).
Wu further teaches the first polypeptide (a) comprises in order (N- to C-terminus; i.e. fused): an antigen binding domain (defined to include antibody based recognition domains (¶ [0077]), which are further defined include fragments or multispecific antibodies (¶ [0040]-[0041])), a hinge region, a transmembrane domain, a first costimulatory domain, and a first member of a dimerizer-binding pair; and the second polypeptide (b) comprises in order (N- to C-terminus; i.e. fused): a transmembrane domain, a second costimulatory domain, a second member of the dimerizer-binding pair, and an intracellular signaling domain (¶ [0091]-[0092]; Figure 17 - shown below).
PNG
media_image1.png
448
522
media_image1.png
Greyscale
Wu teaches said CAR can be utilized in a method of treating cancer comprising genetically modifying patient derived T cells with an expression vector comprising nucleotide sequences encoding the heterodimeric, conditionally active CAR, wherein the antigen-binding domain is specific for an epitope expressed on a cancer cell (e.g. anti-CD19 - Example 1; anti-mesothelin - Example 2) in the individual, introducing the CAR modified T cells (i.e. cells expressing the dimerizer pair) into the patient and administering to the patient a dimerizing agent that induces dimerization of the conditionally active CAR, wherein activation results in killing of the targeted cancer cell (e.g. carcinoma) (¶ [00220] - [00221]). Wu also teaches dimerizer CAR nucleic acid sequences “Construct #197” with an antigen binding domain (scFv) fused to extracellular spacer/hinge and transmembrane domain derived from CD8 fused with a 4-1BB intracellular costimulatory domain and dimerizer element 1 (i.e. Component I and first nucleic acid sequence) (Figures 8A and 8B) and separate nucleic acid sequence for corresponding dimer partner “Construct # 206” containing dimerizer element 2 fused to a intracellular signaling domain derived from CD3 zeta (i.e. Component II) (Figures 9A-C).
While Wu teaches a blue light sensitive dimerizer pair (Cry2 and CIB1 - ¶ [00152]) as a suitable functional equivalent to the explicitly generated FKBP-FRB rapamycin-based dimerization pair, Wu does not teach optogenetic dimerizer pair species recited in the instant claim.
Kennedy teaches CIBN as functional truncation of CIB1 (Figure 1a) and teaches both Cry2-CIB1 and Cry2-CIBN dimerize similarly with blue light exposure (461nm) (Figure 1b). Kennedy further teaches minimal domains (i.e. smaller overall sequence length) can increase packaging efficiency in viral vectors (pg 975, left column, last ¶).
One of ordinary skill in the art would recognize that FKBP-FRB and Cry2-CIBN are functional equivalents as (1) Wu teaches FKBP-FRB and Cry2-CIB1 are suitable alternatives for dimerization pairs within a conditionally active CAR (i.e. suitable equivalents known for the same purpose of forming a dimerization pair with specific trigger; See MPEP 2144.06), and (2) Kennedy further teaches that Cry2-CIB1 and Cry2-CIBN are functional equivalents known for the same purpose (i.e. both dimerize with blue light exposure) (See MPEP 2144.06). Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that the FKBP-FRB dimerizer par within the conditionally active chimeric antigen receptor as taught by Wu could be substituted for a Cry2-CIBN dimerizer pair as taught by Kennedy with a reasonable expectation of success. Moreover a skilled artisan would be motivated to use CIBN over CIB1 as the second dimer since the truncated CIBN would produce an overall smaller construct for higher transfection efficiency as taught by Kennedy.
Response to Arguments - 35 USC § 103
Applicant's arguments filed 11/15/2025 have been fully considered in so far as they apply to the modified rejections above, but they are not persuasive.
Applicant states:
“Applicant respectfully submits that combination of Wu et al. and Ying et al. entail modifications with unpredictable outcome and an ordinary skilled person in the art would not
enjoy a reasonable expectation of success. No ordinary skilled person in the art could have
reasonably expected or predicted the synergistic effect first disclosed in the present application. Undue experimentation would be needed to be carried out.
The mere fact that references can be combined or modified does not render the
resultant combination obvious unless the results would have been predictable to one of
ordinary skill in the art. KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1396
(2007). Rejections on obviousness 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. KSR, 550 U.S. at 418, 82 USPQ2d at 1396 quoting In re
Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).” (Remarks, page 11)
Applicant’s argument regarding specific dimer species is not persuasive because the scope of the respective claims have been amended to exclude previous embodiments referenced in the prior art of record. As applicant has altered the scope of the claims, new ground of rejection are made in view of newly found prior art reference Kennedy, which teaches a dimer pair with demonstrated functional equivalence to a known suitable alternative taught by Wu as discussed above. Moreover, an express suggestion to substitute one equivalent component (e.g. CIB1 for CIBN) or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Conclusion
No claims are allowed.
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 HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647