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 .
Status of Claims
Claims filed on February 26, 2024 is acknowledged. Claims 1-19 are pending and under consideration.
Priority
Acknowledgment is made of applicant's claim for priority based on a US Provisional Application
No. 62/587,201 filed on 11/16/2017.
Terminal Disclaimer
The terminal disclaimer filed on August 04, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 11,649,509 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Drawings
The drawings are objected to because 37 CFR 1.84(c) states “Each drawing sheet submitted after the filing date of an application must be identified as either "Replacement Sheet" or "New Sheet" pursuant to § 1.121(d).”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The following descriptions for FIGs in the Brief Description of the Drawings recite colors in the FIGs:
page 4, lines 5-11, FIG. 1B: “white arrow” and FIG. 1D: “confocal images of the caspase biosensor (green, top panel); Merged images of Hoechst0stained nucleus (blue) and mitochondria (red)”
page 5, line 10, FIG. 3J: “Arrows indicate nuclear GFP expressing in the nurse cells (black), oocyte (white) and follicle cells (yellow)”
It would be remedial to amend the specification to describe the figures without recitation of color and to amend the drawings to indicate different components or events in the cells without relying on usage of color.
Appropriate correction is required.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 10-19 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-9 of prior U.S. Patent No. 11,649,509. This is a statutory double patenting rejection.
Regarding instant claims 10-18, ‘509 claims 1-9 recite identical subject matter.
Regarding instant claim 19, it recites a biosensor comprising a polypeptide of claim 10 and a reporter system. Claim 10 is a polypeptide comprising SEQ ID NO: 2. ‘509 recites identical subject matter in patented claim 10 “an apoptosis biosensor comprising a polypeptide of claim 1 and reporter system”, and patented claim 1 is “a polypeptide comprising SEQ ID NO: 2”. Thus, claim 19, dependent of claim 10 is rejected under 35 U.S.C. 101.
Allowable Subject Matter
Claims 1-9 allowed. Claims 1-9 are directed to polynucleotide comprising specific SEQ ID NOs that encode polypeptides in patented claims 1-9 of U.S. Patent No. 11,649,509 (Terminal Disclaimer filed on August 04, 2026).
Claim 19, depending on claims 11-18, is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claim 19, depending on claims 11-18, is drawn to a biosensor comprising a polypeptide of specific SEQ ID NOs in patented claims 1-9 of U.S. Patent No. 11,649,509 (Terminal Disclaimer filed on August 04, 2026).
The following claim 19 drafted by the examiner and considered to distinguish patentably over the art of record in this application, is presented to applicant for consideration: a biosensor comprising a polypeptide and a reporter system, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, and SEQ ID NO: 40.
The following is a statement of reasons for the indication of allowable subject matter:
The instant claims are drawn to biosensors comprising polypeptides consisting of specific SEQ ID NO. that are recited in parent Application No. 16/763,849 or U. S. Patent No. 11,649,509. The Examiner has aligned the sequences of instantly claimed polypeptides by their domains:
SEQ ID NO: 4: Lyn11-NES-ERT2-DEVD-rtTA-3xFLAG-DEVD-ERT2-NES minus the gca codon at end of 3x flag
SEQ ID NO: 28: Lyn11-NES-ERT2-DEVD-rtTA (with flexible linker following Lyn11)
SEQ ID NO: 30: Lyn11-NES- DEVD-rtTA
SEQ ID NO: 32: Lyn11-NES-ERT2-DEVD-rtTA-3xFLAG
SEQ ID NO: 34: Lyn11-NES- DEVD-rtTA-3xFLAG
SEQ ID NO: 36: ERT2-DEVD-rtTA-3xFLAG-DEVD-ERT2
SEQ ID NO: 38: ERT2-DEVD-rtTA-3xFLAG-DEVD-ERT2 NT w/out GCA after flag
SEQ ID NO: 40: MCD8-NES- DEVD-rtTA
wherein:
Lyn11 is a plasma membrane localization domain
NES is a nuclear exclusion/export signal
ERT2 is estrogen ligan binding domain
DEVD is caspase cleavage site
rtTA is reverse tetracycline transactivator
FLAG is a purification tag
MCD8 is a transmembrane domain from CD8.
Closest prior art: Montell (WO 2013/134499 A1; Published Date: Sept 12, 2013) teaches a biosensor comprising a transmembrane domain (e.g., mCD8), a nuclear export signal (NES), a caspase cleavage site (e.g., DEVD), and a transcriptional activator (e.g., Gal4) (claims 1, 6, and 7; pg. 3, lines 16-24). Montell teaches the biosensor further comprises a reporter system that comprises (1) an activating sequence that binds Gal4, which is operably linked to a first nucleic acid encoding flippase, and (2) a second nucleic acid comprising an flippase-flanked stop cassette separating a constitutive promoter and a fluorescent protein open reading frame (claim 6). Montell further teaches that prior to caspase activation during cell apoptosis, the transcriptional activator Gal4 is tethered to the plasma membrane via a caspase-cleavable linker DEVD peptide and a transmembrane domain mCD8. Upon caspase activation, the DEVD peptide is cleaved, Gal4 is released and translocated to the nucleus to bind to the activating sequence in the reporter system, leading to expression of flippase, which then turns on recombination and expression of the fluorescent protein to record the caspase activation event (pg. 22, lines 20-31; FIG. 5 reproduced below).
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However, the prior art does not teach or suggest instantly claimed polypeptides comprising multiple modular constructs as shown above. Instant claims are drawn to a split transcription factor wherein the split N- and C-terminal fragments are tethered to the transmembrane domain and mitochondria via a caspase-cleavable linker, whereupon cleavage, the split fragments come together to form a functional transcription factor and act on the reporter system (pg. 9, lines 21-30). This Examiner agrees with reasoning of the Examiner for parent Application No. 16/763,849 or U. S. Patent No. 11,649,509 that one of ordinary skilled in the art could not have arbitrarily synthesize polypeptide sequences and use them by trial and error to study the reversibility of apoptosis by analogy with Montell to arrive at the claimed invention. The teachings of Montell do not reach or suggest to swap transcriptional activator Gal4 to instantly claimed rtTA, and/or to flank the transcriptional activator with estrogen ligand binding domain ERT2 to arrive at instant fusion polypeptides for a biosensor to detect and study cell apoptosis.
Conclusion
Claims 1-9 are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIWEN SU-TOBON whose telephone number is (571)272-0331. The examiner can normally be reached Monday - Friday, 9:30am - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/QIWEN SU-TOBON/
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights