43DETAILED 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 .
Response to Amendment
The Amendment filed 03/16/2026 in which claims 1, 2, 4-9, 27, 28, 31, 35, 36,
were amended, has been entered. Claims 2, 7-10 and 35-40 were previously withdrawn. Claims 3, 11-26, 29-30 were previously canceled.
Claims 1, 4-6, 27, 28, 31-34, 41 and 42 are under examination on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 03/16/2026 after the Nonfinal Office Action mailed on 10/16/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 03/16/2026 have overcome the objection previously set forth in the Non-Final Office Action mailed 10/16/2025.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification submitted on 03/16/2026 have overcome the objection previously set forth in the Non-Final Office Action mailed 10/16/2025.
Claim Objections
(Previous objections, withdrawn as to claims 1, 6). Applicant’s amendments to claims 1, 6 have overcome previous objections to claims 1, 6.
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.
(Previous rejection, withdrawn as to 1, 4-6, 27, 28, 31-34, 41 and 42) Claims 1, 4-6, 27, 28, 31-34, 41 and 42 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second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.
See claims 1, 4-6, 27, 28, 31-34, 41 and 42 as submitted on 03/16/2026.
Applicant’s amendment to the instant claims filed on 03/16/2026 has overcome previous rejection to claims 1, 4-6, 27, 28, 31-34, 41 and 42.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(Previous rejection, maintained and modified as necessitated by amendment as to claims 1, 5, 6, and 41) Claims 1, 5, 6, 41 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US Bradbury et al. (prior art of record).
See instant claims 1, 5, 6, 41 as submitted on 03/16/2026.
Regarding amended claim 1, it is noted that the amended claim recites “a green fluorescent protein (GFP) protein structure” and “ wherein the GFP has a beta barrel structure”. However, these limitations are already taught by Bradbury et al. Specifically, Bradbury et al. teach a fluorescent scaffold or carrier protein or fluorobody comprising a GFP protein with a β-barrel structure (¶ [0029]) which is stable and comprises more than four exogenous amino acid sequences (peptides), wherein the GFP has and the peptides were inserted simultaneously at pre-defined positions between strands in the β-barrel at loops 2, 3 and 6 and wherein the fluorescent scaffold or carrier protein can function as a binding ligand (Abstract, ¶¶ [0011]-[0021], Example 1 ¶ [0148], Figs. 1-2). Accordingly, Bradbury et al. anticipate amended claim 1 as submitted on 03/16/2026.
Regarding claims 5 and 6, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. § 112(b), second paragraph and or objections set forth in the Non-Final Office Action mailed on 10/16/2025. No new limitations were introduced in the amendment filed on 03/16/2026. Accordingly, the rejection under 35 U.S.C. § 103 set forth in the previous Non-Final Office Action mailed on 10/16/2025 still applies to amended claims 5 and 6. As previously explained, Bradbury et al. disclose pre-defined insertion sites between strands in the β-barrel at loops 2, 3 and 6, wherein the loops are exposed to the surface of one face of the protein and can function as binding sites, and wherein the fluorescent protein can be fully expressed while retaining its autofluorescence and functioning as a binding ligand (¶¶ [0011]-[0021], [0037], [0085]).
Regarding claim 41, it is noted that no amendments were introduced to claim 41 in the amendment filed on 03/16/2026. As previously explained, Bradbury et al. further disclose a kit comprising the protein of claim 1 for use in diagnostic applications (¶ [0140]).
Accordingly, the rejections of claims 1, 5, 6, 41 are maintained for reasons of record.
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.
(Previous rejection, maintained as to claim 4) Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Bradbury et al., as applied to claims 1, 5, 6, 47 above, in view of Close et al. (prior art of record).
See instant claim 4 as submitted on 03/16/2026.
Regarding claim 4, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. § 112(b), second paragraph set forth in the Non-Final Office Action mailed on 10/16/2025. No new limitations were introduced in the amendment filed on 03/16/2026. Accordingly, the rejection under 35 U.S.C. § 103 set forth in the previous Non-Final Office Action mailed on 10/16/2025 still applies to amended claim 4. As previously explained Bradbury et al. teach the receptacle protein of claim 1. Bradbury et al. do not teach an animo acid sequence at least 90% identical to SEQ ID NO: 77.
However, Close et al. teach a thermal green protein (TGP), an extremely stable, highly soluble, non-aggregating green fluorescent protein that can be used as a carrier protein for expression of exogenous proteins in various assays (Abstract, pages 1-3). Close et al. further teach an amino acid sequence for TGP available on the Worldwide Protein Data Bank (wwPDB) with accession number 4TZA (page 4) which shares 100% sequence identity with instant SEQ ID NO: 77. See alignment below (Qy is instant SEQ ID NO: 77, Db is Close et al.’s 4TZA sequence).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the amino acid sequence of TGP taught by Close et al. into the receptacle protein of Bradbury et al for the benefit of formulating an extremely stable, highly soluble, non-aggregating green fluorescent protein that can be used as a carrier protein for expression of exogenous proteins. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the amino acid sequence of TGP of Close et al. as the receptacle protein of Bradbury et al. given that the methods of cloning fluorescent proteins are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
PNG
media_image1.png
692
655
media_image1.png
Greyscale
Accordingly, the limitations of amended claim 4 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 03/16/2026 have been fully considered but they are not persuasive.
Applicant contends on pages 12-13 of the Remarks submitted on 03/16/2026:
“This disclosure is insufficient to anticipate the claimed subject matter, at least because Bradbury discloses that this report was retracted, and only includes examples having two or three exogenous sequences. Regarding this 2003 report, the retraction document (see attached) makes it clear that the research group was unable to obtain functional fluorobodies from the simultaneous insertion of 3 or 4 exogenous peptides into the GFP loops, as initially described in the paper. Thus, this paper, besides not anticipating the matter in question, actually demonstrates the difficulty of generating GFP clones that maintain the barrel conformation when attaching 3-4 exogenous peptides, further demonstrating the patentability of the claimed subject matter. Accordingly, for at least the above reasons, Applicant respectfully submits that the rejection based on 35 U.S.C. 102 is improper.”
In response:
As explained above, Example 1 (¶¶ [0148], [0149], Figs. 1-2) of Bradbury et al. teach more than four insertion sites within loops 2, 3 and 6 of a GFP sequence for the insertion of exogenous peptides and wherein the GFP protein retains function. Figs. 1 and 2 of Bradbury et al. specifically refer to more than four sites of insertion within loops 2, 3 and 6 of the GFP sequence as well as peptides ranging from 3-14 amino acids long for insertion in those pre-determined insertion sites (¶¶ [0148], [0149]). It is noted that the embodiments of Bradbury et al. are not limited to three insertions, Bradbury et al. specifically teach insertion of peptides in “at least three loops”, wherein at least one of those loops comprises multiple insertion sites (Bradbury et al., claims 1, 4-5; Figs 1-2). Accordingly, the teachings of Bradbury et al. already disclose the protein receptacle of instant claim 1. With respect to Applicant’s argument of a retracted 2003 study mentioned in the introduction of Bradbury et al.’s patent application. These remarks are unpersuasive for the following reasons. First the 2003 study was not cited in the rejections of record. Second, retraction of a study, (which incidentally was originally conducted by a different inventorship entity), does not provide any evidence that the disclosure of Bradbury et al. does not anticipate the instant claims. The retraction of a study is irrelevant to the instant rejections. Third, any evidence demonstrating difficulty in generating GFP clones as claimed does not serve as evidence that Bradbury et al. does not anticipate the instant claims. Alleged difficulty in arriving at the claimed protein receptacle itself is irrelevant to the instant rejections. The instant rejections are in view of instant claim language. Although the claims are interpreted in light of the Specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Accordingly, it is maintained that Bradbury et al. anticipate instant claims.
Applicant contends on page 16 of the Remarks submitted on 03/16/2026:
“Firstly, Applicant respectfully submits that claim 4 is patentable at least due to its
dependency on claim 1, which Applicant submits is patentable for at least the above reasons. Additionally, even if the sequence of Close has 100% homology to SEQ ID NO: 77, this is insufficient to satisfy claim 4, because the sequence of Close lacks any exogenous amino acid sequences. Thus, the combination of Bradbury and Close merely discloses SEQ ID NO: 77 as a 'base' sequence, with two or three exogenous amino acid sequences added. Since the claims require at least four exogenous sequences, claim 4 is patentable over the cited art. In other words, Close fails to make up for the deficiencies of Bradbury. Accordingly, Applicant respectfully submits that claim 4 is patentable over the cited art for at least this reason. Favorable reconsideration is respectfully requested.
In response:
To reiterate, the instant rejections are in view of instant claim language. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claim 4 requires an animo acid sequence at least 90% identical to SEQ ID NO: 77. Close et al. teach a sequence which shares 100% sequence identity with instant SEQ ID NO: 77.
Applicant contends on page 16 of the Remarks submitted on 03/16/2026:
“Applicant respectfully declines to rewrite any of the allowable dependent claims into independent form at this time.”
In response:
Applicant’s remarks regarding rewriting of the allowable claims is herein acknowledged. It is also acknowledged that the Examiner noted claim 41 instead of claim 42 as allowable if rewritten to overcome the rejections set forth in the Non-Final Office Action mailed on 10/16/2025. Claim 42 is the correct claim.
Conclusion
Claims 27, 28, 31-34, 42 remain 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.
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-R 8:00 AM - 5:00 PM.
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, Thomas J. Visone can be reached on (571)270-0684. 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.
/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
Prosecution Insights