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 .
Election/Restrictions
Applicant’s election of the invention of Group I, claims 1-22, and the species of SEQ ID NO: 3038, SEQ ID NO: 3037, SEQ ID NO: 3034, SEQ ID NO: 1188, SEQ ID NO: 3078, and SEQ ID NO: 3110 in the reply filed on 05/18/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
The amendment of 05/18/2026 has been entered. Claims 1-22 are currently pending in this US patent application and were examined on their merits.
Information Disclosure Statement
The information disclosure statement filed in this application on 05/21/2025 has been received and considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that SEQ ID NOs: 3034 and 3035 contain no information. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
Claims 10-11 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.
Applicant has elected SEQ ID NO: 3034 as the peptide component of the modified dehalogenase complex. However, as noted above, the listing of SEQ ID NO: 3034 provided in the instant application contains no information. As such, the Examiner cannot ascertain what sequence is represented by SEQ ID NO: 3034, which renders the claims reciting this sequence indefinite. Therefore, claims 10-11 are rejected under 35 U.S.C. 112(b).
In the interest of compact prosecution, the Examiner has interpreted the peptide component of the modified dehalogenase complex in the instant claims, including claims 10-11, to be any peptide component of a modified dehalogenase complex.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-22 are rejected under 35 U.S.C. 103 as being unpatentable over US patent application publication 2010/0273186 filed by Wood, published 10/28/2010, in view of US patent application publication 2008/0145882 filed by Darzins et al., published 06/19/2008, and US patent application publication 2014/0348747 filed by Dixon et al., published 11/27/2014.
Wood teaches a system having two fragments of a hydrolase with an N- or C-terminus at a residue corresponding to a residue in a region including residue 14-24 of a dehalogenase, which may be a DhaA (see entire document, including paragraph 0014). The N- and/or C-terminus of the hydrolase fragment may include deletions relative to the sequence of a corresponding full-length mutant or wild-type hydrolase or may be fused to a heterologous amino acid sequence, such as hydrolase sequences found in one of the hydrolase fragments that interact with a molecule of interest (paragraph 0014). In certain embodiments, the heterologous amino acids sequences interact, yielding a complex of the two fusion proteins under certain conditions but not under other conditions (paragraph 0015). In certain embodiments, the heterologous amino acid sequence is a fragment of a luciferase (paragraph 0016; cf. claim 22). An exemplary substrate for the dehalogenase is an alkyl halide linked to a fluorophore (paragraphs 0158-0159; cf. claims 19-20). Substrates with luminescent and fluorescent functional groups may be used in interaction studies such as BRET (paragraph 0124; cf. claims 18-19 and 21; the Examiner notes that bioluminescence resonance energy transfer, or BRET, intrinsically requires the use of a luminophore that emits light at a wavelength that excites the fluorophore). The mutant dehalogenase may form a covalent bond with its substrate (paragraphs 0022 and 0168; cf. claim 1).
However, Wood does not teach that the fragments of the dehalogenase and luciferase are the dehalogenase and luciferase sequences recited in the instant claims and elected by Applicant.
Darzins teaches mutant hydrolase enzymes with improved functional expression and/or intrinsic binding kinetics (see entire document, including paragraph 0006). SEQ ID NO: 27 of Darzins recites a 297-residue polypeptide. Residues 22-297 of this polypeptide have 100% identity with instant SEQ ID NO: 1188 and a portion of SEQ ID NO: 3110, and residues 3-19 of this polypeptide have 100% identity with the first 19 amino acids of instant SEQ ID NO: 3078 (cf. claims 1 and 10-17; see above under Claim Rejections – 35 USC 112 for the Examiner’s interpretation of SEQ ID NO: 3034). The mutant hydrolases are variants of DhaA (paragraph 0113).
Dixon teaches the assembly of a bioluminescent complex from two or more non-luminescent peptide and/or polypeptide units (see entire document, including paragraph 0002). The polypeptide sequence SEQ ID NO: 440, which is equivalent to instant SEQ ID NO: 3037 and a portion of SEQ ID NO: 3110, of Dixon produces luminescence when it contacts one of the peptides of Table 1, of which one is SEQ ID NO: 390 (paragraphs 0195 and 0198; Table 1), which is equivalent to instant SEQ ID NO: 3038 and to the final 11 amino acids of instant SEQ ID NO: 3078 (cf. claims 1, 3, 6-9, and 14-17). Dixon’s bioluminescent complexes are derived from luciferase enzymes (paragraph 0194).
While Wood does not explicitly teach fragments with an N- or C-terminus at a residue corresponding to a residue in a region including residue 14-24 of DhaA, it would have been obvious to one of ordinary skill in the art to do so because Wood suggests constructing such fragments, along with the other structural elements cited above. One of ordinary skill in the art would have a reasonable expectation that protein fragments made according to the suggestions of Wood would successfully result in the production of protein fragments that are capable of performing the dehalogenase reporting function described by Wood.
While Wood does not teach using the DhaA variant of Darzins and the bioluminescent complex of Dixon in the reporter fusion protein containing fragments of a DhaA dehalogenase enzyme that complement one another fused to fragments of a bioluminescent complex that also complement one another, it would have been obvious to one of ordinary skill in the art to do so because Wood teaches that the dehalogenase may be a DhaA, and Darzins teaches DhaA variants that have improved properties. Similarly, Wood teaches that the DhaA fragments may be fused to fragments of a luciferase, and Dixon teaches fragments of luciferase variants that complement one another structurally and produce luminescence when brought together. One of ordinary skill in the art would have a reasonable expectation that using the DhaA of Darzins and the bioluminescent complex of Dixon in the dehalogenase reporter of Wood would successfully result in the production of a dehalogenase reporter capable of producing both fluorescence and luminescence. The Examiner notes that doing so would intrinsically result in the production of the tandem peptide tag and tandem polypeptide reporter elected by Applicant and recited in instant claims 14-17 and 22 that have the properties recited in instant claims 2-5. Regarding instant claim 22, the Examiner notes that the instant specification indicates that peptides are an example of “target elements” (page 5, line 10), and so the tandem peptide tag rendered obvious by the teachings of Wood, Darzins, and Dixon would intrinsically contain “a target element” as recited in instant claim 22.
Therefore, claims 1-22 are rendered obvious by Wood and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau, can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 07/23/2026
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