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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/23/2026 has been entered.
Claims 12, 21-29 and 31 are pending.
This application is a continuation of PCT/US19/46764, filed August 16, 2019, which claims priority to U.S. Provisional Application No. 62/765,129, filed on August 16, 2018, and U.S. Provisional Application No. 62/798,206, filed January 29, 2019.
Response to Amendments
The response is sufficient to overcome the objections as well as rejections under 35 USC 112, second.
The terminal disclaimers filed on 3/23/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent 12,509,498 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Objections
Claims 21 and 26 are objected to because of the following informalities: upon a more thorough read, it appears that the article “the” is required in line 7 of claim 12, prior to “second”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 12, 22 and 24-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong et al (WO 2017/091546) as evidenced by Hussack et al (Frontiers in Immunology, 2017, pages 1-11) and as evidenced by Brown et al (PLOS ONE, 2013, pages 1-10). This rejection is maintained for reasons of record.
There are two parts of the system of Wong et al that anticipate the system of the claims. The claimed system comprises first, a first expression vector encoding a membrane bound peptide with an extracellular domain. The EC comprises two dimerization domains that comprise a leucine zipper domain from orthogonal zippers. Orthogonal zippers are described in the disclosure ¶ 0104, In certain embodiments, the first and second leucine zipper domains of the membrane-bound polypeptide are a pair of orthogonal zippers, i.e., the first and the second leucine zipper domains are the specific partners for each other to form heterodimers. However, one of the orthogonal partners will also bind to a third dimerization domain. But, this format is displayed in Wong et al in figure 16.
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BZip1 and BZip2 are orthogonal as set forth in the disclosure (see e.g. ¶00206) and BZip1 can bind to AZip. ¶0204 which states, Two orthogonal BZIP zippers can be attached onto a zipCAR.
Hence, Wong teaches a system comprising the claimed constructs and these are on vectors (¶00138). The constructs comprise antibodies which as established by Hussack et al antibodies are tags (page 12).
When pure to very pure proteins are needed ABTAG can be used as a purification tag for BSA-affinity matrix purification. When the efficacy of a protein needs to be evaluated in vivo, the protein-ABTAG can be mixed with BSA to overcome the limitation of short serum half-life of the protein
As to claim 22, in ¶00212 a linker is used between the zippers which encompasses claims 22 as well as claim 26 as claim 26 is a description of one of the choices of claim 22 and hence the limitations are only relevant if a TNF, Ig, co-stimulatory ligand, immune checkpoint molecule or TNFRSF is selected from claim 22. Since Wong teaches a liner, the remaining choices are moot. However, it is noted that the membrane bound protein comprises a 4-1BB peptide (see ¶00276).
In figure 3C, CD3z is attached to the membrane bound polypeptide as recited in claim 24 and claim 25.
As recited in claims 27-29, the B-Zip CAR comprises an mCherry or my epitope tag. Epitope tags are recognized by specific antibodies allowing for their detection and analysis. These are placed on the extracellular domain (see Brown et al).
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 12 and 21-29 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al (WO 2017/091546) as evidenced by Hussack et al (Frontiers in Immunology, 2017, pages 1-11) and as evidenced by Brown et al (PLOS ONE, 2013, pages 1-10) in view of Lim et al (US 20160264665). This rejection is maintained for reasons of record.
While Wong et al do not provide the sequences of the BZips, they are known in the art and presented below.
RESULT 5
US-15-096-971-68
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 68, US/15096971
Patent No. 9670281
GENERAL INFORMATION
APPLICANT: Lim, Wendell A.
APPLICANT: Morsut, Leonardo
APPLICANT: Roybal, Kole T.
TITLE OF INVENTION: BINDING-TRIGGERED TRANSCRIPTIONAL SWITCHES AND METHODS OF USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: UCSF-511WO
CURRENT APPLICATION NUMBER: US/15/096,971
CURRENT FILING DATE: 2016-04-12
PRIOR APPLICATION NUMBER: US 62/120,256
PRIOR FILING DATE: 2015-02-24
PRIOR APPLICATION NUMBER: US 62/257,153
PRIOR FILING DATE: 2015-11-18
PRIOR APPLICATION NUMBER: US 62/269,758
PRIOR FILING DATE: 2015-12-18
NUMBER OF SEQ ID NOS: 210
SEQ ID NO 68
LENGTH: 205
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Synthetic polypeptide
Query Match 100.0%; Score 233; Length 205;
Best Local Similarity 100.0%;
Matches 47; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LEIRAAFLRQRNTALRTEVAELEQEVQRLENEVSQYETRYGPLGGGK 47
|||||||||||||||||||||||||||||||||||||||||||||||
Db 1 LEIRAAFLRQRNTALRTEVAELEQEVQRLENEVSQYETRYGPLGGGK 47
RESULT 3
US-15-096-971-67
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 67, US/15096971
Patent No. 9670281
GENERAL INFORMATION
APPLICANT: Lim, Wendell A.
APPLICANT: Morsut, Leonardo
APPLICANT: Roybal, Kole T.
TITLE OF INVENTION: BINDING-TRIGGERED TRANSCRIPTIONAL SWITCHES AND METHODS OF USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: UCSF-511WO
CURRENT APPLICATION NUMBER: US/15/096,971
CURRENT FILING DATE: 2016-04-12
PRIOR APPLICATION NUMBER: US 62/120,256
PRIOR FILING DATE: 2015-02-24
PRIOR APPLICATION NUMBER: US 62/257,153
PRIOR FILING DATE: 2015-11-18
PRIOR APPLICATION NUMBER: US 62/269,758
PRIOR FILING DATE: 2015-12-18
NUMBER OF SEQ ID NOS: 210
SEQ ID NO 6729
LENGTH: 109
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Synthetic polypeptide
Query Match 100.0%; Score 233; Length 109;
Best Local Similarity 100.0%;
Matches 47; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LEIEAAFLERENTALETRVAELRQRVQRLRNRVSQYRTRYGPLGGGK 47
|||||||||||||||||||||||||||||||||||||||||||||||
Db 63 LEIEAAFLERENTALETRVAELRQRVQRLRNRVSQYRTRYGPLGGGK 109
Similarly, linkers for use in multimer ZIP domains, (GGGS)3 i.e. SEQ ID NO:3. This arrangement is shown in Mori on page 695, col 2, ¶3.
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 include sequences as claimed in products referencing these sequences by name. As noted above: 1) Wong teaches use of ZIP domains and linkers but does not provide for the sequences; 2) as set forth above, these sequences are known and provided for in the art. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that one could make and use the product given the ability to construct the products from the art.
Response to Arguments
Applicants argue that the characterization of Wong is incorrect. Specifically, applicants argue that while the paragraphs make clear that the BZIPs can be orthogonal, figure 16 does not demonstrate dimerization of BZIP1 and BZIP2 but with the AZIPs on the zipFvs. Applicants continue in the response to the 103 rejection that the incorporation of an orthogonal pair as shown in Figure 16 would render Wong inoperative for its intended purpose. Secondly, applicants argue that the instant invention provides specific and unexpected benefits by allowing dimer formation only in the same cell and by increasing stringency.
As to the first argument, that the BZIPs can be orthogonal is enough as that is all that is required of the first expression vector. The diagrams in Figure 16 need not show the BZIPs interacting to prove this as these are depictions of the structure. That they are orthogonal is sufficient as that is all that is required of the constructs of the claims. Applicants appear to be arguing that by orthogonal the claims are indicating that the Bzips are orthogonal to the Azips. However, this is not the construction of the disclosure which states clearly that two orthogonal Bzips are added to the CAR.
As to the second argument, the unexpected results are not commensurate with the claims. Applicants assert but do not dhow that the claimed invention has properties that would not have been expected in the art. The 103 is simply showing the sequences one would expect as they are known in the art. Applicants results of unexpected results would have to demonstrate that using those sequences would have led to unexpected properties. This requires actual results and not arguments.
Conclusion
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/MARIA MARVICH/Primary Examiner, Art Unit 1634