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 .
1. The Election filed July 1, 2026, in response to the Office Action of May 1, 2026, is acknowledged. Applicant elected with traverse Group II, claims 10, 11, 13-21, and 37.
2. Applicant argues that Group II is directed to a dimerization-dependent reporter system, including embodiments corresponding to the PAR-T GFP and related reporter platforms extensively described and experimentally validated throughout the specification. Applicant argues that Group II also includes numerous dependent claims directed to specific PAR-binding domains (e.g., AF1521 macrodomains and RNF 146 WWE domains), exclusions of PBZ domains, and kit claims, thereby providing multiple fallback positions during prosecution.
3. The arguments have been considered but are not persuasive. Applicants have not persuasively argued against the technical feature linking Groups I-V as a first fusion protein comprising a first reporter protein functionally linked to a first poly-ADP ribose binding moiety and/or a second fusion protein comprising a second reporter protein functionally linked to a second poly-ADP ribose binding moiety. Applicants have not persuasively argued that Ghosh (US Patent Application Publication 2009/0170069) does not teach the shared technical feature of the restricted Groups. Further, the limitations of dependent claims argued by Applicants are not a shared technical feature across the restricted Groups. Ghosh teaches the technical feature linking the inventions of Groups I-V, therefore the technical feature does not constitute a special technical feature as defined by PCT Rule 13.2 as it does not define a contribution over the prior art. Accordingly, Groups I-V are not so linked by the same or a corresponding special technical feature as to form a single general inventive concept and restriction for examination purposes as indicated is proper.
For these reasons, the restriction requirement is deemed to be proper and is therefore made FINAL.
4. Claims 1, 2, 4, 10, 11, 13-26, 37 are pending. Claims 1, 2, 4, 22-26 have been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions. Claims 10, 11, 13-21, and 37 are currently under prosecution.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 13 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 13 recites: “wherein the first and/or second monomers are operably linked to a second fluorescent protein”. No first fluorescent protein was recited in the claims, therefore it is unclear how there can be a second. Claim 14 also refers to the second fluorescent protein. Clarification is required.
Claim Rejections - 35 USC § 102
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.
6. Claim(s) 10, 11, 13, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent Application Publication 2009/0170069, Ghosh.
Ghosh discloses a split reporter system for detecting poly-ADP ribose polymerase (PARP) activity comprising:
(a) a first fusion protein comprising a first monomer of a dimerization-dependent reporter system functionally linked to a first poly-ADP ribose binding moiety (PNK-like factor (APLF)), and
(b) a second fusion protein comprising a second monomer of the dimerization-dependent reporter system functionally linked to a second poly-ADP ribose binding moiety (APLF);
wherein the first and second monomers of the dimerization dependent reporter system are capable of combining to form a heterodimer of the dimerization-dependent reporter system, the heterodimer capable of emitting a detectable light signal (APLF-NFluc and CFluc-APLF) (claim 1; [0173]; Figure 25).
Alternative to labeling with split-luciferase, Ghosh teaches the first and second poly-ADP ribose binding moieties can be labeled with other split-reporter (dimerization-dependent) signals such as split Venus GFP ([20]; [48]; [50]; [66]; [122]; [161]; Figure 1(b)).
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.
7. Claim(s) 10, 11, 13-21 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application Publication 2009/0170069, Ghosh in view of WO 2022/234194, Lehtiö et al (claiming priority to May 6, 2021); and US Patent Application Publication 2015/0355172, Kraus et al.
Ghosh teaches the dimerization-dependent split reporter system for detecting poly-ADP ribose polymerase (PARP) activity comprising first and second poly-ADP ribose binding moieties (APLF) fused to a dimerization-dependent split reporter (split luciferase or GFP), as set forth above.
Ghosh does not teach the first and/or second poly-ADP ribose binding moiety:
Is a macro domain derived from ADP ribose glycohydrolase AF1521 comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:1 (claims 15-17); and/ or
Is a WWE domain from RNF146 E3 ligase having at least 80% sequence identity to SEQ ID NO:2 (claims 18-20); or
Lacks a PBZ domain having an amino acid sequence comprising SEQ ID NO:3 (i.e., APLF) (claim 21).
Ghosh does not teach the first or second fusion proteins are comprised in a kit with a container (claim 37).
Lehtiö teaches a dual reporter system for detecting poly-ADP ribose polymerase (PARP) activity that comprises a poly-ADP ribose binding moiety linked to a reporter molecule,
wherein the poly-ADP ribose binding moiety can be the PBZ domain of APLF, the WWE domain of E3 ubiquitin ligase, or a macro domain such as AF1521 (p. 1-3, 12-13, 17; Figures 1 and 4; Example 1; claims 1, 8, 9, 34)
wherein the reporter molecule is luciferase (i.e., Nanoluc-eAF1521), GFP, YFP, or CFP (p. 7-8, 11, 17-18; Figures 1 and 4; Example 1; claims 14-15, 26, 30, 32, 34, 38, 39).
Lehtiö teaches kits comprising the detectably labeled poly-ADP ribose binding moiety and container (p. 3-4, 11; claims 17, 24 and 25).
Kraus teaches a reporter system for detecting poly-ADP ribose polymerase (PARP) activity that comprises a fusion protein comprising a poly-ADP ribose binding moiety and a detectable reporter molecule,
wherein the poly-ADP ribose binding moiety is SEQ ID NO:2 that contains macro molecule AF1521 with 100% identity to instant SEQ ID NO:1 (see sequence alignment below) (Figures 1, 3, 6, and 8; [10]; [17]; [39-45]; [47]; Examples 1-3; claims 1, 8, 13, 21, 26, 27, 29-31);
wherein the poly-ADP ribose binding moiety is SEQ ID NO:1 that contains WWE domain of RNF146 E3 ligase that is 100% identical to instant SEQ ID NO:2 except it is missing the first methionine of instant SEQ ID NO:2 (see sequence alignment below) (Figures 1, 3, and 8; [10]; [17]; [35]; [39-46]; Examples 1-3; claims 1, 8, 13, 21, 26, 27, 29-31); and
wherein detectable reporter molecules include GFP ([94-96]; [186]; [190]; [197-201]).
Kraus further teaches kits comprising the fusion protein and containers such as vials ([232-237]).
Substitute the APLF poly-ADP ribose binding moiety of Ghosh with the WEE domain and/or AF1521 macro domain of Lehtiö and Kraus
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to utilize the WEE domain and/or AF1521 macro domain of Lehtiö and Kraus as the poly-ADP ribose binding moiety in the reporter system of Ghosh. One would have been motivated to, and have a reasonable expectation of success to, because: (1) all of the cited references teach detecting poly-ADP ribose utilizing a detectably labeled poly-ADP ribose binding moiety; (2) the cited references teach APLF, WEE SEQ ID NO:2, and macro domain AF1521 SEQ ID NO:1 serve the same function as a detectably labeled poly-ADP ribose binding moiety for poly-ADP ribose detection, identifying and demonstrating they all are functionally equivalent; and Lehtiö suggests the poly-ADP ribose binding moiety can be any of APLF, WEE, and AF1521. Given the cited prior art teaches and demonstrates using any of APLF, WEE domain SEQ ID NO:2, and macro domain AF1521 SEQ ID NO:1 to bind and detect poly-ADP ribose, one of skill in the art could have substituted one known poly-ADP ribose binding moiety for another (i.e., substituting the WEE domain or AF1521 macro domain into the APLF domain of Ghosh), and the results of producing a fusion protein that is a detectably labeled poly-ADP ribose binding moiety comprising WEE domain or AF1521 macro domain for the detection of poly-ADP ribose would have been predictable.
Poly-ADP ribose binding moiety lacks PBZ domain SEQ ID NO:3
Given the obviousness rationale provided above to substitute the APLF poly-ADP ribose binding moiety of Ghosh with the WEE domain and/or AF1521 macro domain of Lehtiö or Kraus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to exclude the use of APLF PBZ domain SEQ ID NO:3 because the WEE domain and/or AF1521 macro domain of Lehtiö or Kraus do not comprise PBZ domain SEQ ID NO:3.
Kit comprising the fusion proteins and containers:
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to provide a kit comprising the fusion proteins of the combined cited references and containers. One would have been motivated to, and have a reasonable expectation of success to, because Lehtiö and Kraus teach and suggest packaging the detectably labeled poly-ADP ribose binding moieties in a kit with containers for storage and use.
Instant AF1521 SEQ ID NO:1 aligned with Kraus SEQ ID NO:2
RESULT 1
US-14-734-780-2
Sequence 2, US/14734780
Publication No. US20150355172A1
GENERAL INFORMATION
APPLICANT: The Board of Regents of the University of Texas System
TITLE OF INVENTION: ADP-RIBOSE DETECTION REAGENTS
FILE REFERENCE: UTSD.P2725US
CURRENT APPLICATION NUMBER: US/14/734,780
CURRENT FILING DATE: 2015-06-09
PRIOR APPLICATION NUMBER: US 62/009,955
PRIOR FILING DATE: 2014-06-10
NUMBER OF SEQ ID NOS: 11
SEQ ID NO 2
LENGTH: 460
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Synthetic fusion peptide
Query Match 100.0%; Score 1005; Length 460;
Best Local Similarity 100.0%;
Matches 199; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MERRTLIMEVLFEAKVGDITLKLAQGDITQYPAKAIVNAANKRLEHGGGVAYAIA KACAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 33 MERRTLIMEVLFEAKVGDITLKLAQGDITQYPAKAIVNAANKRLEHGGGVAYAIA KACAG 92
Qy 61 DAGLYTEISKKAMREQFGRDYIDHGEVVVTPAMNLEERGIKYVFHTVGPICSGMWSEELK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93 DAGLYTEISKKAMREQFGRDYIDHGEVVVTPAMNLEERGIKYVFHTVGPICSGMWSEELK 152
Qy 121 EKLYKAFLGPLEKAEEMGVESIAFPAVSAGIYGCDLEKVVETFLEAVKNFKGSAVKEVAL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 153 EKLYKAFLGPLEKAEEMGVESIAFPAVSAGIYGCDLEKVVETFLEAVKNFKGSAVKEVAL 212
Qy 181 VIYDRKSAEVALKVFERSL 199
|||||||||||||||||||
Db 213 VIYDRKSAEVALKVFERSL 231
Instant WWE SEQ ID NO:2 aligned with Kraus SEQ ID NO:1
RESULT 3
US-14-734-780-1
Sequence 1, US/14734780
Publication No. US20150355172A1
GENERAL INFORMATION
APPLICANT: The Board of Regents of the University of Texas System
TITLE OF INVENTION: ADP-RIBOSE DETECTION REAGENTS
FILE REFERENCE: UTSD.P2725US
CURRENT APPLICATION NUMBER: US/14/734,780
CURRENT FILING DATE: 2015-06-09
PRIOR APPLICATION NUMBER: US 62/009,955
PRIOR FILING DATE: 2014-06-10
NUMBER OF SEQ ID NOS: 11
SEQ ID NO 1
LENGTH: 349
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Synthetic fusion peptide
Query Match 98.9%; Score 451; Length 349;
Best Local Similarity 100.0%;
Matches 83; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GNGEYAWYYEGRNGWWQYDERTSRELEDAFSKGKKNTEMLIAGFLYVADLENMVQYRRNE 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 36 GNGEYAWYYEGRNGWWQYDERTSRELEDAFSKGKKNTEMLIAGFLYVADLENMVQYRRNE 95
Qy 62 HGRRRKIKRDIIDIPKKGVAGLR 84
|||||||||||||||||||||||
Db 96 HGRRRKIKRDIIDIPKKGVAGLR 118
8. Conclusion: No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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, Samira Jean-Louis can be reached at 571-270-3503. 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.
/Laura B Goddard/Primary Examiner, Art Unit 1642
Prosecution Insights